Butyryl-cholinesterase is related to muscle mass and strength. A new biomarker to identify elderly subjects at risk of sarcopenia.

Science.gov (United States)

Cacciatore, Francesco; Della-Morte, David; Basile, Claudia; Curcio, Francesco; Liguori, Ilaria; Roselli, Mario; Gargiulo, Gaetano; Galizia, Gianluigi; Bonaduce, Domenico; Abete, Pasquale

2015-01-01

To determine the relationship between Butyryl-cholinesterase (α-glycoprotein synthesized in the liver, b-CHE) and muscle mass and strength. Muscle mass by bioimpedentiometer and muscle strength by grip strength were evaluated in 337 elderly subjects (mean age: 76.2 ± 6.7 years) admitted to comprehensive geriatric assessment. b-CHE levels were lower in sarcopenic than in nonsarcopenic elderly subjects (p elderly subjects. Thus, b-CHE may be considered to be a fair biomarker for identifying elderly subjects at risk of sarcopenia.

BRAIN CHOLINESTERASE INHIBITION AND DEPRESSION OF THE PHOTIC AFTER DISCHARGE (PHAD) OF FLASH EVOKED POTENTIALS (FEPS) IN LONG EVANS RATS FOLLOWING ACUTE OR REPEATED EXPOSURES TO A MIXTURE OF CARBARYL AND PROPOXUR.

Science.gov (United States)

Carbaryl and propoxur are N-methyl carbamate pesticides (NMCs) which are part of the EPA’s cumulative risk assessments for NMCs. These NMCs inhibit cholinesterase (ChE) activity and may lead to cholinergic disruption of CNS function. We used decreases in the PhAD of FEPs to indic...

Evolution of cholinesterases in the animal kingdom.

Science.gov (United States)

Pezzementi, Leo; Chatonnet, Arnaud

2010-09-06

Cholinesterases emerged from a family of enzymes and proteins with adhesion properties. This family is absent in plants and expanded in multicellular animals. True cholinesterases appeared in triploblastic animals together with the cholinergic system. Lineage specific duplications resulted in two acetylcholinesterases in most hexapods and in up to four genes in nematodes. In vertebrates the duplication leading to acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is now considered to be an ancient event which occurred before the split of osteichthyes. The product of one or the other of the paralogues is responsible for the physiological hydrolysis of acetylcholine, depending on the species lineage and tissue considered. The BChE gene seems to have been lost in some fish lineages. The complete genome of amphioxus (Branchiostoma floridae: cephalochordate) contains a large number of duplicated genes or pseudogenes of cholinesterases. Sequence comparison and tree constructions raise the question of considering the atypical ChE studied in this organism as a representative of ancient BChE. Thus nematodes, arthropods, annelids, molluscs, and vertebrates typically possess two paralogous genes coding for cholinesterases. The origin of the duplication(s) is discussed. The mode of attachment through alternative C-terminal coding exons seems to have evolved independently from the catalytic part of the gene. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Plasma Cholinesterase Activity in Female Green Turtles Chelonia mydas Nesting in Laguna de Terminos, Mexico Related to Organochlorine Pesticides in Their Eggs.

Science.gov (United States)

Rivas-Hernández, Gerardo; May-Uc, Yaneli; Noreña-Barroso, Elsa; Cobos-Gasca, Víctor; Rodríguez-Fuentes, Gabriela

2018-01-01

The inhibition of cholinesterase (ChE) activity has been used as a biomarker of exposure to organophosphate and carbamate insecticides. ChE of nesting female green turtles (Chelonia mydas) were biochemically characterized using two substrates, acetylthiocholine iodide and butyrylthiocholine iodide, and three ChE inhibitors (eserine sulfate, BW284C51 and iso-OMPA). The results indicated that BChE is the predominant plasma ChE in female C. mydas, but with atypical properties that differ from those found in human BChE. Eggs from green turtles nesting at two sites in Laguna de Terminos contained µg g -1 (wet weight) quantities of organochlorine (OC) pesticides. Drins (aldrin, dieldrin, endrin, endrin ketone, endrin aldehyde) were found at the highest concentrations with no significant differences in the concentrations in eggs collected at the two sampling sites. A negative relationship was found between levels of OC pesticides in eggs and BChE activity in the plasma of female turtles laying the eggs. Since OC pesticides are not cholinesterase inhibitors, we hypothesized that this inverse relationship may be related to an antagonistic effect between OCs and organophosphate pesticides and mobilization of OCs from the fatty tissues of the female turtles into their eggs. However, further study is required to verify the hypothesis. It is also possible that other contaminants, such as petroleum hydrocarbons are responsible for the modulation of cholinesterase activity in female turtles.

Development of square wave voltammetry method for the assessment of organophosphorus compound impact on the cholinesterase of Pheretima with 2,6-dichloroindophenol as a redox indicator.

Science.gov (United States)

Qiu, Jingxia; Chen, Jin; Ma, Qianqian; Miao, Yuqing

2009-09-01

A square wave voltammetry method was developed for the assessment of organophosphorus (OPs) compound impact on the cholinesterase of Pheretima with 2,6-dichloroindophenol (2,6-DCIP) as a redox indicator. The substrate of acetylthiocholine is hydrolysed by the cholinesterase (ChE) from soil animal pheretima, and the produced thiocholine reacts with the 2,6-DCIP to give obvious shift of electrochemical signal. The inhibition of ChE was assessed by measuring the enzyme activity before and after incubating with parathion-methyl. The reduction peak current of 2,6-DCIP decreases with the time of enzymatical reaction. The ChE loses almost 32.74% activity after 10 min incubation with 1ng mL(-1) paraoxon and 54.62% with 10 microg mL(-1) paraoxon, while the activity that corresponds to 100 microg mL(-1) paraoxon was nearly completely inhibited. This method can be employed to assess the inhibition of ChE and investigate OPs impact on environmental animals.

Early appearance and possible roles of non-neuromuscular cholinesterases.

Directory of Open Access Journals (Sweden)

Carla eFalugi

2012-04-01

Full Text Available The biological function of the cholinesterase (ChE enzymes is well known and has been studied since the beginning of the XXth century; in particular, acetylcholinesterase (AChE, E.C. 3.1.1.7 is an enzyme playing a key role in the modulation of neuromuscular impulse transmission. However, in the past decades, there has been increasing interest concerning its role in regulating non-neuromuscular cell-to-cell interactions mediated by intracellular ion concentration changes, like the ones occurring during gamete interaction and embryonic development. An understanding of the mechanisms of the cholinergic regulation of these events can help us foresee the possible impact on environmental and human health, including gamete efficiency and possible teratogenic effects on different models, and help elucidate the extent to which exposure to ChE inhibitors may affect human health.

Characterization of the In Vitro Kinetic Interaction of Chlorpyrifos-Oxon with Rat Salivary Cholinesterase: A Potential Biomonitoring Matrix

Energy Technology Data Exchange (ETDEWEB)

Kousba, Ahmed A.(BATTELLE (PACIFIC NW LAB)); Poet, Torka S.(BATTELLE (PACIFIC NW LAB)); Timchalk, Charles (Pacific Northwest National Laboratory)

2003-02-12

Chlorpyrifos (CPF) is a commonly used organophosphate insecticide (OP). The primary mechanism of action for CPF involves the inhibition of acetylcholinesterase (AChE) by the active metabolite, CPF-oxon, with subsequent accumulation of acetylcholine (ACh) resulting in a wide range of neutotoxicity. CPF-oxon, can likewise inhibit other non-target cholinesterases (ChE) such as butyrylcholinesterase (BuChE), which represents a detoxification mechanism and a potential biomarker of exposure/response. Biological monitoring for OPs has focused on measuring parent chemical or metabolite in blood and urine or blood ChE inhibition. Salivary biomonitoring has recently been explored as a practical method for examination of chemical exposure; however, there are a limited number of studies exploring its use for OPs. To evaluate the use of salivary ChE as a biological monitor for OP exposure, the current study characterized salivary ChE activity in Sprague-Dawley rats through its comparison with brain and plasma ChE using BW284C51 and iso-OMPA as selective inhibitors of AChE and BuChE, respectively. The study also estimated the kinetic constants describing BuChE interaction with CPF-oxon. A modified Ellman assay in conjunction with pharmacodynamic (PD) modeling was used to characterize the in vitro titration of diluted rat salivary ChE enzyme with CPF-oxon. The results indicated that, more than 95% of rat salivary ChE activity was associated with BuChE activity, total BuChE active site concentration was 0.0012 0.00013 nmol/ml saliva, reactivation rate constant (Kr) was 0.068 0.008 h-1 and inhibitory (Ki) rate constant of 8.825 and 9.80 nM-1h-1 determined experimentally and using model optimization respectively. These study results would be helpful for further evaluating the potential utility of salivary ChE as a practical tool for biological monitor of OP exposures.

In Search of an Effective in vivo Reactivator for Organophosphorus Nerve Agent-Inhibited Acetylcholinesterase in the Central Nervous System

Science.gov (United States)

2012-01-01

nerve agents, such as sarin (GB), cyclosarin (GF), and VX, are potent inhibitors of the enzyme cholinesterase (ChE). Their toxic effects are due to...three nerve agents. Keywords: acetylcholinesterase; brain; cholinesterase inhibition; cholinesterase reactivation; cyclosarin; diacetylmonoxime...attributed, at least in part, to nuclophilic impedance [Ekstrom et al., 2006a; b; Hoskovcova et al., 2007]. Other AChE- inhibitors , such as soman, become

Characterization of catalytic efficiency parameters of brain cholinesterases in tropical fish.

Science.gov (United States)

de Assis, Caio Rodrigo Dias; Linhares, Amanda Guedes; Oliveira, Vagne Melo; França, Renata Cristina Penha; Santos, Juliana Ferreira; Marcuschi, Marina; Carvalho, Elba Verônica Matoso Maciel; Bezerra, Ranilson Souza; Carvalho, Luiz Bezerra

2014-12-01

Brain cholinesterases from four fish (Arapaima gigas, Colossoma macropomum, Rachycentron canadum and Oreochromis niloticus) were characterized using specific substrates and selective inhibitors. Parameters of catalytic efficiency such as activation energy (AE), k(cat) and k(cat)/k(m) as well as rate enhancements produced by these enzymes were estimated by a method using crude extracts described here. Despite the BChE-like activity, specific substrate kinetic analysis pointed to the existence of only acetylcholinesterase (AChE) in brain of the species studied. Selective inhibition suggests that C. macropomum brain AChE presents atypical activity regarding its behavior in the presence of selective inhibitors. AE data showed that the enzymes increased the rate of reactions up to 10(12) in relation to the uncatalyzed reactions. Zymograms showed the presence of AChE isoforms with molecular weights ranging from 202 to 299 kDa. Values of k(cat) and k(cat)/k(m) were similar to those found in the literature.

Development of Cholinesterase Inhibitors Using (a)-Lipoic Acid-benzyl Piperazine Hybrid Molecules

International Nuclear Information System (INIS)

Kim, Beomcheol; Lee, Seunghwan; Jang, Mi; Shon, Min Young; Park, Jeong Ho

2013-01-01

A series of hybrid molecules between (α)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE (IC 50 = 2.3 ± 0.7 μM) and AChE (IC 50 = 30.31 ± 0.64 μM). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity (K i ) value to BuChE is 2.91 ± 0.15 μM

Multitarget-directed tricyclic pyridazinones as G protein-coupled receptor ligands and cholinesterase inhibitors.

Science.gov (United States)

Pau, Amedeo; Catto, Marco; Pinna, Giovanni; Frau, Simona; Murineddu, Gabriele; Asproni, Battistina; Curzu, Maria M; Pisani, Leonardo; Leonetti, Francesco; Loza, Maria Isabel; Brea, José; Pinna, Gérard A; Carotti, Angelo

2015-06-01

By following a multitarget ligand design approach, a library of 47 compounds was prepared, and they were tested as binders of selected G protein-coupled receptors (GPCRs) and inhibitors of acetyl and/or butyryl cholinesterase. The newly designed ligands feature pyridazinone-based tricyclic scaffolds connected through alkyl chains of variable length to proper amine moieties (e.g., substituted piperazines or piperidines) for GPCR and cholinesterase (ChE) molecular recognition. The compounds were tested at three different GPCRs, namely serotoninergic 5-HT1A, adrenergic α1A, and dopaminergic D2 receptors. Our main goal was the discovery of compounds that exhibit, in addition to ChE inhibition, antagonist activity at 5-HT1A because of its involvement in neuronal deficits typical of Alzheimer's and other neurodegenerative diseases. Ligands with nanomolar affinity for the tested GPCRs were discovered, but most of them behaved as dual antagonists of α1A and 5-HT1A receptors. Nevertheless, several compounds displaying this GPCR affinity profile also showed moderate to good inhibition of AChE and BChE, thus deserving further investigations to exploit the therapeutic potential of such unusual biological profiles. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of Cholinesterase Inhibitors Using (a)-Lipoic Acid-benzyl Piperazine Hybrid Molecules

Energy Technology Data Exchange (ETDEWEB)

Kim, Beomcheol; Lee, Seunghwan; Jang, Mi; Shon, Min Young; Park, Jeong Ho [Hanbat National Univ., Daejeon (Korea, Republic of)

2013-11-15

A series of hybrid molecules between (α)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE (IC{sub 50} = 2.3 ± 0.7 μM) and AChE (IC{sub 50} = 30.31 ± 0.64 μM). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity (K{sub i}) value to BuChE is 2.91 ± 0.15 μM.

Cholinesterase Inhibition and Depression of the Photic After Discharge of Flash Evoked Potentials Following Acute or Repeated Exposures to a Mixture of Carbaryl and Propoxur

Science.gov (United States)

While information exists regarding inhibition of cholinesterase (ChE) activity, little is known about neurophysiological changes produced by a mixture of N-methyl carbamate pesticides. Previously, we reported that acute treatment with propoxur or carbaryl decreased the duration o...

Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors.

Science.gov (United States)

Tsurkan, Lyudmila G; Hatfield, M Jason; Edwards, Carol C; Hyatt, Janice L; Potter, Philip M

2013-03-25

Carboxylesterases (CEs) are ubiquitously expressed proteins that are responsible for the detoxification of xenobiotics. They tend to be expressed in tissues likely to be exposed to such agents (e.g., lung and gut epithelia, liver) and can hydrolyze numerous agents, including many clinically used drugs. Due to the considerable structural similarity between cholinesterases (ChE) and CEs, we have assessed the ability of a series of ChE inhibitors to modulate the activity of the human liver (hCE1) and the human intestinal CE (hiCE) isoforms. We observed inhibition of hCE1 and hiCE by carbamate-containing small molecules, including those used for the treatment of Alzheimer's disease. For example, rivastigmine resulted in greater than 95% inhibition of hiCE that was irreversible under the conditions used. Hence, the administration of esterified drugs, in combination with these carbamates, may inadvertently result in decreased hydrolysis of the former, thereby limiting their efficacy. Therefore drug:drug interactions should be carefully evaluated in individuals receiving ChE inhibitors. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Impaired recovery of brain muscarinic receptor sites following an adaptive down-regulation induced by repeated administration of diisopropyl fluorophosphate in aged rats

International Nuclear Information System (INIS)

Pintor, A.; Fortuna, S.; De Angelis, S.; Michalek, H.

1990-01-01

Potential age-related differences in the recovery rate of brain cholinesterase activity (ChE) and muscarinic acetylcholine receptor binding sites (mAChRs) following reduction induced by repeated treatment with diisopropyl fluorophosphate (DFP) were evaluated in Sprague-Dawley rats. Male 3- and 24-month old rats were s.c. injected with DFP on alternate days for 2 weeks and killed 48 hr and 7, 14, 21, 28 and 35 days after the last treatment. In the hippocampus and striatum, but not in the cerebral cortex, of control rats there as a significant age-related decline of ChE activity and maximal density of 3H-QNB binding sites (Bmax). The repeated administration of DFP during the first week caused a syndrome of cholinergic stimulation both in aged and young rats. The syndrome was more pronounced, in terms of intensity and duration in aged than in young animals resulting in 40 and 12% mortality, respectively; during the second week the syndrome attenuated in the two age-groups. The percentage inhibition of brain ChE at the end of DFP treatment did not differ between young and surviving aged rats. The down-regulation of mACRs was present in the three brain regions of both young and age rats (from 20 to 40%). Factorial analysis of variance showed significant differences for age, recovery rate, and significant interaction between age and recovery rate, both for ChE and mAChRs in young rats the three brain areas

Impaired recovery of brain muscarinic receptor sites following an adaptive down-regulation induced by repeated administration of diisopropyl fluorophosphate in aged rats

Energy Technology Data Exchange (ETDEWEB)

Pintor, A.; Fortuna, S.; De Angelis, S.; Michalek, H. (Istituto Superiore di Sanita, Rome (Italy))

1990-01-01

Potential age-related differences in the recovery rate of brain cholinesterase activity (ChE) and muscarinic acetylcholine receptor binding sites (mAChRs) following reduction induced by repeated treatment with diisopropyl fluorophosphate (DFP) were evaluated in Sprague-Dawley rats. Male 3- and 24-month old rats were s.c. injected with DFP on alternate days for 2 weeks and killed 48 hr and 7, 14, 21, 28 and 35 days after the last treatment. In the hippocampus and striatum, but not in the cerebral cortex, of control rats there as a significant age-related decline of ChE activity and maximal density of 3H-QNB binding sites (Bmax). The repeated administration of DFP during the first week caused a syndrome of cholinergic stimulation both in aged and young rats. The syndrome was more pronounced, in terms of intensity and duration in aged than in young animals resulting in 40 and 12% mortality, respectively; during the second week the syndrome attenuated in the two age-groups. The percentage inhibition of brain ChE at the end of DFP treatment did not differ between young and surviving aged rats. The down-regulation of mACRs was present in the three brain regions of both young and age rats (from 20 to 40%). Factorial analysis of variance showed significant differences for age, recovery rate, and significant interaction between age and recovery rate, both for ChE and mAChRs in young rats the three brain areas.

Excitant and depressant drugs modulate effects of environment on brain weight and cholinesterases

Energy Technology Data Exchange (ETDEWEB)

Bennett, E.L.; Rosenzweig, M.R.; Wu, S.Y.C.

1973-01-01

Certain excitant drugs can enhance the effects of enriched experience on weights of brain sections and on the activities of acetylcholinesterase and cholinesterase in the brain, and certain depressants can lessen the brain weight effects. Most experiments were performed with prepubertal male rats. Some rats were exposed in groups of 12 to an enriched environmental condition (EC), usually for 2 h per day and over a 30-day period; others remained in their individual home cages (HC) throughout. Some received a drug injection and others received a saline injection before the daily EC period; HC controls received similar injections. The drug injections had no significant effects on brain values of HC rats, but they altered effects of EC, probably by influencing the animals' reactions to the environment. Methamphetamine and d-amphetamine enhanced the EC effects; metrazol had small positive effects; and strychnine was without effects. Phenobarbital depressed the brain weight effects but increased the enzymatic effects. Use of methamphetamine made it possible to find EC effects with short daily periods (30 min) or with a shortened experimental duration (15 days). In experiments with adult rats, methamphetamine did not modulate the brain weight effects. The results of this study may bear on the use of stimulants to promote recovery from brain damage.

In vivo and in vitro changes in neurochemical parameters related to mercury concentrations from specific brain regions of polar bears (Ursus maritimus).

Science.gov (United States)

Krey, Anke; Kwan, Michael; Chan, Hing Man

2014-11-01

Mercury (Hg) has been detected in polar bear brain tissue, but its biological effects are not well known. Relationships between Hg concentrations and neurochemical enzyme activities and receptor binding were assessed in the cerebellum, frontal lobes, and occipital lobes of 24 polar bears collected from Nunavik (Northern Quebec), Canada. The concentration-response relationship was further studied with in vitro experiments using pooled brain homogenate of 12 randomly chosen bears. In environmentally exposed brain samples, there was no correlative relationship between Hg concentration and cholinesterase (ChE) activity or muscarinic acetylcholine receptor (mAChR) binding in any of the 3 brain regions. Monoamine oxidase (MAO) activity in the occipital lobe showed a negative correlative relationship with total Hg concentration. In vitro experiments, however, demonstrated that Hg (mercuric chloride and methylmercury chloride) can inhibit ChE and MAO activities and muscarinic mAChR binding. These results show that Hg can alter neurobiochemical parameters but the current environmental Hg exposure level does have an effect on the neurochemistry of polar bears from northern Canada. © 2014 SETAC.

Brain cholinesterase response in the snakehead fish (Channa striata) after field exposure to diazinon

DEFF Research Database (Denmark)

van Cong, Nguyen; Phuong, Nguyen Thanh; Bayley, Mark

2008-01-01

The snakehead Channa striata is an economically important air-breathing fish species in the Mekong delta of Vietnam. Rice paddies, which are disturbed by the frequent application of agro-chemicals, are among the preferred habitats for this species during the rainy season. Diazinon is one of most...... commonly used chemicals in rice paddies. In the present study, exposure of adult snakehead fish to a single diazinon application in cages within a rice field resulted in long-term brain cholinesterase inhibition, while the water concentration of this insecticide fell below the detection limit within 3 days...

Muscarinic receptor plasticity in the brain of senescent rats: down-regulation after repeated administration of diisopropyl fluorophosphate

International Nuclear Information System (INIS)

Pintor, A.; Fortuna, S.; Volpe, M.T.; Michalek, H.

1988-01-01

Potential age-related differences in the response of Fischer 344 rats to subchronic treatment with diisopropylfluorophosphate (DFP) were evaluated in terms of brain cholinesterase (ChE) inhibition and muscarinic receptor sites. Male 3- and 24-month old rats were sc injected with sublethal doses of DFP for 2 weeks and killed 48 hrs after the last treatment. In the cerebral cortex, hippocampus and striatum of control rats a significant age-related reduction of ChE and of maximum number of 3 H-QNB binding sites (Bmax) was observed. The administration of DFP to senescent rats resulted in more pronounced and longer lasting syndrome of cholinergic stimulation, with marked body weight loss and 60% mortality. The percentage inhibition of brain ChE induced by DFP did not differ between young and senescent rats. As expected, in young rats DFP caused a significant decrease of Bmax, which in the cerebral cortex reached about 40%. In the surviving senescent rats, the percentage decrease of Bmax due to DFP with respect to age-matched controls was very similar to that of young animals, especially in the cerebral cortex. Thus there is great variability in the response of aged rats to DFP treatment, from total failure of adaptive mechanisms resulting in death to considerable muscarinic receptor plasticity

Muscarinic receptor plasticity in the brain of senescent rats: down-regulation after repeated administration of diisopropyl fluorophosphate

Energy Technology Data Exchange (ETDEWEB)

Pintor, A.; Fortuna, S.; Volpe, M.T.; Michalek, H.

1988-01-01

Potential age-related differences in the response of Fischer 344 rats to subchronic treatment with diisopropylfluorophosphate (DFP) were evaluated in terms of brain cholinesterase (ChE) inhibition and muscarinic receptor sites. Male 3- and 24-month old rats were sc injected with sublethal doses of DFP for 2 weeks and killed 48 hrs after the last treatment. In the cerebral cortex, hippocampus and striatum of control rats a significant age-related reduction of ChE and of maximum number of /sup 3/H-QNB binding sites (Bmax) was observed. The administration of DFP to senescent rats resulted in more pronounced and longer lasting syndrome of cholinergic stimulation, with marked body weight loss and 60% mortality. The percentage inhibition of brain ChE induced by DFP did not differ between young and senescent rats. As expected, in young rats DFP caused a significant decrease of Bmax, which in the cerebral cortex reached about 40%. In the surviving senescent rats, the percentage decrease of Bmax due to DFP with respect to age-matched controls was very similar to that of young animals, especially in the cerebral cortex. Thus there is great variability in the response of aged rats to DFP treatment, from total failure of adaptive mechanisms resulting in death to considerable muscarinic receptor plasticity.

Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophosphate nerve agent exposure

Energy Technology Data Exchange (ETDEWEB)

Halbrook, R.S.; Shugart, L.R.; Watson, A.P.; Munro, N.B.; Linnabary, R.D. (Environmental Sciences Division, Oak Ridge National Laboratory, TN (United States))

1992-09-01

A biomonitoring protocol, using blood cholinesterase (ChE) activity in livestock as a monitor of potential organophosphate nerve agent exposure during the planned destruction of US unitary chemical warfare agent stockpiles, is described. The experimental design included analysis of blood ChE activity in individual healthy sheep, horses, and dairy and beef cattle during a 10- to 12-month period. Castrated and sexually intact males, pregnant and lactating females, and adult and immature animals were examined through at least one reproductive cycle. The same animals were used throughout the period of observation and were not exposed to ChE-inhibiting organophosphate or carbamate compounds. A framework for an effective biomonitoring protocol within a monitoring area includes establishing individual baseline blood ChE activity for a sentinel group of 6 animals on the bases of blood samples collected over a 6-month period, monthly collection of blood samples for ChE-activity determination during monitoring, and selection of adult animals as sentinels. Exposure to ChE-inhibiting compounds would be suspected when all blood ChE activity of all animals within the sentinel group are decreased greater than 20% from their own baseline value. Sentinel species selection is primarily a logistical and operational concern; however, sheep appear to be the species of choice because within-individual baseline ChE activity and among age and gender group ChE activity in sheep had the least variability, compared with data from other species. This protocol provides an effective and efficient means for detecting abnormal depressions in blood ChE activity in livestock and can serve as a valuable indicator of the extent of actual plume movement and/or deposition in the event of organophosphate nerve agent release.

Hydroxybenzoic Acid Derivatives as Dual-Target Ligands: Mitochondriotropic Antioxidants and Cholinesterase Inhibitors.

Science.gov (United States)

Oliveira, Catarina; Cagide, Fernando; Teixeira, José; Amorim, Ricardo; Sequeira, Lisa; Mesiti, Francesco; Silva, Tiago; Garrido, Jorge; Remião, Fernando; Vilar, Santiago; Uriarte, Eugenio; Oliveira, Paulo J; Borges, Fernanda

2018-01-01

Alzheimer's disease (AD) is a multifactorial age-related disease associated with oxidative stress (OS) and impaired cholinergic transmission. Accordingly, targeting mitochondrial OS and restoring cholinergic transmission can be an effective therapeutic strategy toward AD. Herein, we report for the first time dual-target hydroxybenzoic acid (HBAc) derivatives acting as mitochondriotropic antioxidants and cholinesterase (ChE) inhibitors. The studies were performed with two mitochondriotropic antioxidants AntiOxBEN 1 (catechol derivative), and AntiOxBEN 2 (pyrogallol derivative) and compounds 15-18 , which have longer spacers. Compounds AntiOxBEN 1 and 15 , with a shorter carbon chain spacer (six- and eight-carbon) were shown to be potent antioxidants and BChE inhibitors (IC 50 = 85 ± 5 and 106 ± 5 nM, respectively), while compounds 17 and 18 with a 10-carbon chain were more effective AChE inhibitors (IC 50 = 7.7 ± 0.4 and 7.2 ± 0.5 μM, respectively). Interestingly, molecular modeling data pointed toward bifunctional ChEs inhibitors. The most promising ChE inhibitors acted by a non-competitive mechanism. In general, with exception of compounds 15 and 17 , no cytotoxic effects were observed in differentiated human neuroblastoma (SH-SY5Y) and human hepatocarcinoma (HepG2) cells, while Aβ-induced cytotoxicity was significantly prevented by the new dual-target HBAc derivatives. Overall, due to its BChE selectivity, favorable toxicological profile, neuroprotective activity and drug-like properties, which suggested blood-brain barrier (BBB) permeability, the mitochondriotropic antioxidant AntiOxBEN 1 is considered a valid lead candidate for the development of dual acting drugs for AD and other mitochondrial OS-related diseases.

Hydroxybenzoic Acid Derivatives as Dual-Target Ligands: Mitochondriotropic Antioxidants and Cholinesterase Inhibitors

Directory of Open Access Journals (Sweden)

Catarina Oliveira

2018-04-01

Full Text Available Alzheimer's disease (AD is a multifactorial age-related disease associated with oxidative stress (OS and impaired cholinergic transmission. Accordingly, targeting mitochondrial OS and restoring cholinergic transmission can be an effective therapeutic strategy toward AD. Herein, we report for the first time dual-target hydroxybenzoic acid (HBAc derivatives acting as mitochondriotropic antioxidants and cholinesterase (ChE inhibitors. The studies were performed with two mitochondriotropic antioxidants AntiOxBEN1 (catechol derivative, and AntiOxBEN2 (pyrogallol derivative and compounds 15–18, which have longer spacers. Compounds AntiOxBEN1 and 15, with a shorter carbon chain spacer (six- and eight-carbon were shown to be potent antioxidants and BChE inhibitors (IC50 = 85 ± 5 and 106 ± 5 nM, respectively, while compounds 17 and 18 with a 10-carbon chain were more effective AChE inhibitors (IC50 = 7.7 ± 0.4 and 7.2 ± 0.5 μM, respectively. Interestingly, molecular modeling data pointed toward bifunctional ChEs inhibitors. The most promising ChE inhibitors acted by a non-competitive mechanism. In general, with exception of compounds 15 and 17, no cytotoxic effects were observed in differentiated human neuroblastoma (SH-SY5Y and human hepatocarcinoma (HepG2 cells, while Aβ-induced cytotoxicity was significantly prevented by the new dual-target HBAc derivatives. Overall, due to its BChE selectivity, favorable toxicological profile, neuroprotective activity and drug-like properties, which suggested blood-brain barrier (BBB permeability, the mitochondriotropic antioxidant AntiOxBEN1 is considered a valid lead candidate for the development of dual acting drugs for AD and other mitochondrial OS-related diseases.

Hydroxybenzoic acid derivatives as dual-target ligands: mitochondriotropic antioxidants and cholinesterase inhibitors

Science.gov (United States)

Oliveira, Catarina; Cagide, Fernando; Teixeira, José; Amorim, Ricardo; Sequeira, Lisa; Mesiti, Francesco; Silva, Tiago; Garrido, Jorge; Remião, Fernando; Vilar, Santiago; Uriarte, Eugenio; Oliveira, Paulo J.; Borges, Fernanda

2018-04-01

Alzheimer’s disease (AD) is a multifactorial age-related disease associated with oxidative stress (OS) and impaired cholinergic transmission. Accordingly, targeting mitochondrial OS and restoring cholinergic transmission can be an effective therapeutic strategy towards AD. Herein, we report for the first time dual-target hydroxybenzoic acid (HBAc) derivatives acting as mitochondriotropic antioxidants and cholinesterase (ChE) inhibitors. The studies were performed with two mitochondriotropic antioxidants AntiOxBEN1 (catechol derivative), and AntiOxBEN2 (pyrogallol derivative) and compounds 15-18, which have longer spacers. Compounds AntiOxBEN1 and 15, with a shorter carbon chain spacer (six- and eight-carbon) were shown to be potent antioxidants and BChE inhibitors (IC50 = 85 ± 5 and 106 ± 5 nM, respectively), while compounds 17 and 18 with a ten-carbon chain were more effective AChE inhibitors (IC50 = 7.7 ± 0.4 and 7.2 ± 0.5 nM, respectively). Interestingly, molecular modelling data pointed towards bifunctional ChEs inhibitors. The most promising ChE inhibitors acted by a non-competitive mechanism. In general, with exception of compounds 15 and 17, no cytotoxic effects were observed in differentiated human neuroblastoma (SH-SY5Y) and human hepatocarcinoma (HepG2) cells, while Αβ-induced cytotoxicity was significantly prevented by the new dual-target HBAc derivatives. Overall, due to its BChE selectivity, favourable toxicological profile, neuroprotective activity and drug-like properties, which suggested blood-brain barrier (BBB) permeability, the mitochondriotropic antioxidant AntiOxBEN1 is considered a valid lead candidate for the development of dual acting drugs for AD and other mitochondrial OS-related disease

Acute toxicity and cholinesterase inhibition of the nematicide ethoprophos in larvae of gar Atractosteus tropicus (Semionotiformes: Lepisosteidae

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Freylan Mena Torres

2012-03-01

Full Text Available Biomarkers are a widely applied approach in environmental studies. Analyses of cholinesterase (ChE, glutathione S-transferase (GST and lipid peroxidation (LPO are biomarkers that can provide information regarding early effects of pollutants at different biochemical levels on an organism. The aim of this study was to evaluate the biomarker approach on a Costa Rican native and relevant species. For this, larvae of gar (Atractosteus tropicus were exposed to the organophosphorus nematicide, ethoprophos. Acute (96hr exposure was conducted with pesticide concentrations ranging from 0.1μg/L to 1 500μg/L. The 96hr LC50 calculated was 859.7μg/L. After exposure, three biomarkers (ChE, GST and LPO were analyzed in fish that survived the acute test. The lowest observed effect concentration (LOEC regarding ChE activity inhibition was 50μg/L. This concentration produced a significant inhibition (p0.05 in GST activity and LPO were observed in A. tropicus larvae after exposure to ethoprophos.

Rosemary tea consumption results to anxiolytic- and anti-depressant-like behavior of adult male mice and inhibits all cerebral area and liver cholinesterase activity; phytochemical investigation and in silico studies.

Science.gov (United States)

Ferlemi, Anastasia-Varvara; Katsikoudi, Antigoni; Kontogianni, Vassiliki G; Kellici, Tahsin F; Iatrou, Grigoris; Lamari, Fotini N; Tzakos, Andreas G; Margarity, Marigoula

2015-07-25

Our aim was to investigate the possible effects of regular drinking of Rosmarinus officinalis L. leaf infusion on behavior and on AChE activity of mice. Rosemary tea (2% w/w) phytochemical profile was investigated through LC/DAD/ESI-MS(n). Adult male mice were randomly divided into two groups: "Rosemary-treated" that received orally the rosemary tea for 4weeks and "control" that received drinking water. The effects of regular drinking of rosemary tea on behavioral parameters were assessed by passive avoidance, elevated plus maze and forced swimming tests. Moreover, its effects on cerebral and liver cholinesterase (ChE) isoforms activity were examined colorimetricaly. Phytochemical analysis revealed the presence of diterpenes, flavonoids and hydroxycinnamic derivatives in rosemary tea; the major compounds were quantitatively determined. Its consumption rigorously affected anxiety/fear and depression-like behavior of mice, though memory/learning was unaffected. ChE isoforms activity was significantly decreased in brain and liver of "rosemary treated" mice. In order to explain the tissue ChE inhibition, principal component analysis, pharmacophore alignment and molecular docking were used to explore a possible relationship between main identified compounds of rosemary tea, i.e. rosmarinic acid, luteolin-7-O-glucuronide, caffeic acid and known AChE inhibitors. Results revealed potential common pharmacophores of the phenolic components with the inhibitors. Our findings suggest that rosemary tea administration exerts anxiolytic and antidepressant effects on mice and inhibits ChE activity; its main phytochemicals may function in a similar way as inhibitors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

El humanismo del Che Che's Humanism

OpenAIRE

Avelino Fernández Espert; Cristina Fernández Rivero

2004-01-01

Los autores, estudiosos de la raigal influencia del pensamiento y la obra del Comandante Dr. Ernesto Guevara de la Serna (Che) en Cuba y América, proyectan la estampa humanista de este revolucionario médico, con el empleo de las más trascendentes pinceladas históricas de un amplia hoja de vida en distintas latitudes del mundo. El Che, joven estudiante, médico graduado con prometedoras dotes que sabe ubicar al ser humano y sus valores por encima de un promisorio futuro como científico y profes...

Design, synthesis and evaluation of novel tacrine-coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer's disease.

Science.gov (United States)

Xie, Sai-Sai; Wang, Xiao-Bing; Li, Jiang-Yan; Yang, Lei; Kong, Ling-Yi

2013-06-01

A series of tacrine-coumarin hybrids (8a-t) were designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit ChE and self-induced β-amyloid (Aβ) aggregation, and to act as metal chelators. Especially, 8f displayed the greatest ability to inhibit acetylcholinesterase (AChE, IC50 = 0.092 μM) and Aβ aggregation (67.8%, 20 μM). It was also a good butyrylcholinesterase inhibitor (BuChE, IC50 = 0.234 μM) and metal chelator. Besides, kinetic and molecular modeling studies indicated that 8f was a mixed-type inhibitor, binding simultaneously to active, peripheral and mid-gorge sites of AChE. These results suggested that 8f might be an excellent multifunctional agent for AD treatment. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Long term exposure to low dose neurotoxic pesticides affects hatching, viability and cholinesterase activity of Artemia sp.

Science.gov (United States)

Gambardella, Chiara; Nichino, Daniela; Iacometti, Camillo; Ferrando, Sara; Falugi, Carla; Faimali, Marco

2018-03-01

The brine shrimp Artemia was used as a model organism to test toxicity of several neuroactive pesticides (chlorpyrifos (CLP), chlorpyrifos oxon (CLP ox), diazinon (DZN), carbaryl (CBR)) following exposure to far below than lethal doses. Cysts were exposed to the pesticides in order to test a scenario similar to actual coastal environment contamination, by analyzing different responses. Cysts were rehydrated in water containing the pesticides at concentrations ranging from 10 -11 to 10 -5  M, for 72, 96 and 192 h, respectively. For these exposure times, morpho-functional and biochemical parameters, such as hatching speed and viability were investigated in the larvae together with cholinesterase (ChE) activity quantification and histochemical localization. Finally, ChE inhibition was also compared with conventional selective ChE inhibitors. Results showed that CLP ox and CBR caused a significant dose-dependent decrease in hatching speed, followed by high percentages of larval death, while CLP and DZN were responsible for irregular hatching patterns. In addition, the pesticides mostly caused larval death some days post-hatching, whereas this effect was negligible for the specific ChE inhibitors, suggesting that part of pesticide toxicity may be due to molecules other than the primary target. ChE activity was observed in the protocerebrum lobes, linked to the development of pair eyes. Such activity was inhibited in larvae exposed to all pesticides. When compared to conventional selective inhibitors of ChE activities, this inhibition demonstrated that the selected pesticides mainly affect acetylcholinesterase and, to a lesser extent, pseudocholinesterases. In conclusion, the brine shrimp is a good model to test the environmental toxicity of long term exposure to cholinergic pesticides, since changes in hatching speed, viability and ChE activity were observed. Copyright © 2018 Elsevier B.V. All rights reserved.

Recombinant butyryl-cholinesterase (RBuChe) therapy following VX poisoning by the percutaneous route: preliminary studies

International Nuclear Information System (INIS)

Speakman, P.; Armstrong, S.

2009-01-01

Medical countermeasures to prevent or mitigate the effects of nerve agent poisoning are part of the UK MoD's integrated approach to CBRN defence. Protexia is currently in advanced development as a pretreatment for nerve agent poisoning by PharmAthene in collaboration with US DoD. The principle of its use in this context has been demonstrated in a model of inhalation exposure. Nerve agent poisoning by the percutaneous route poses additional challenges for medical countermeasures. The present study investigates the effects of non-pegylated rBuChE administered following poisoning by VX in an animal model of percutaneous exposure. This investigation is part of an ongoing programme of work assessing the potential of candidate medical interventions. Male guinea pigs implanted with dermal and blood microdialysis probes were maintained under anaesthesia. VX (296 micro g/kg or 740 micro g/kg) was applied to the dorsal skin and non-pegylated rBuChE or placebo was administered (i.v.) 30 minutes later. Dialysate fractions were collected for 8 hours and VX was analysed by LC-MS-MS. Cholinesterase levels were measured in selected tissues post mortem. Following VX (296 micro g/kg), non-pegylated rBuChE significantly reduced the concentration of VX in the blood but had no effect on dermal concentrations; additionally following VX (740 micro g/kg), non-pegylated rBuChE prevented lethality. Tissue cholinesterase activity was inhibited following VX exposure but in those animals treated with rhBuChE, activities were similar to control values. To our knowledge these results provide the first evidence of the mechanism of therapeutic intervention with rBuChE. Further work is necessary to increase confidence in these preliminary observations by conducting confirmatory studies. Crown Copyright 2008. This work was carried out as part of the UK MoD NBC Research Programme. Non-pegylated rBuChE was supplied by PharmAthene under a materials transfer and non-disclosure agreement. (author)

Structural Insight inot the low Affinity Between Thermotoga maritima CheA and CheB Compared to their Escherichia coli/Salmonella typhimurium Counterparts

Energy Technology Data Exchange (ETDEWEB)

S Park; B Crane

2011-12-31

CheA-mediated CheB phosphorylation and the subsequent CheB-mediated demethylation of the chemoreceptors are important steps required for the bacterial chemotactic adaptation response. Although Escherichia coli CheB has been reported to interact with CheA competitively against CheY, we have observed that Thermotoga maritima CheB has no detectable CheA-binding. By determining the CheY-like domain crystal structure of T. maritima CheB, and comparing against the T. maritima CheY and Salmonella typhimurium CheB structures, we propose that the two consecutive glutamates in the {beta}4/{alpha}4 loop of T. maritima CheB that is absent in T. maritima CheY and in E. coli/S. typhimurium CheB may be one factor contributing to the low CheA affinity.

Cholinesterase-based biosensors.

Science.gov (United States)

Štěpánková, Šárka; Vorčáková, Katarína

2016-01-01

Recently, cholinesterase-based biosensors are widely used for assaying anticholinergic compounds. Primarily biosensors based on enzyme inhibition are useful analytical tools for fast screening of inhibitors, such as organophosphates and carbamates. The present review is aimed at compilation of the most important facts about cholinesterase based biosensors, types of physico-chemical transduction, immobilization strategies and practical applications.

Dicty_cDB: CHE636 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available CH (Link to library) CHE636 (Link to dictyBase) - - - Contig-U11696-1 CHE636P (Link... to Original site) CHE636F 174 CHE636Z 123 CHE636P 277 - - Show CHE636 Library CH (Link to library) Clone ID CHE636 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U11696-1 Original site URL http://dict...ne RP11-15H22, WORKING DRAFT SEQUENCE, 23 unordered pieces. 40 0.19 3 AC149612 |AC149612.1 Ictalurus punctat... %: cytoskeletal 4.0 %: mitochondrial >> prediction for CHE636 is nuc 5' end seq. ID CHE636F 5' end seq. >CH

Introduzione. Donne che portano la parrucca

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Claudia Mattalucci-Yılmaz

2013-07-01

Full Text Available Peruk takan kadınlar è l’opera che nel 1999 l’artista e cineasta turco Kutlug Ataman ha presentato alla Biennale di Venezia curata da Harald Szeemann. Quattro schermi giustapposti proiettano le testimonianze di donne che, per un periodo della loro vita, hanno portato una parrucca: un’attivista politica di sinistra che nel 1971, dopo il colpo di stato militare, utilizzava un nome in codice, una divisa delle Turkish Airlines e una parrucca per sfuggire al controllo della polizia; una giornalista, colpita da un tumore al seno, che ha portato una parrucca per mascherare gli effetti della chemioterapia; una studentessa musulmana che indossa una parrucca per frequentare l’università, in un contesto – quello turco – che in nome della laicità dello Stato, interdice l’uso nel foulard nelle scuole, nelle università e nella pubblica amministrazione; e infine un transessuale.

Protease inhibitors and indoleamines selectively inhibit cholinesterases in the histopathologic structures of Alzheimer disease.

Science.gov (United States)

Wright, C I; Guela, C; Mesulam, M M

1993-01-01

Neurofibrillary tangles and amyloid plaques express acetylcholinesterase and butyrylcholinesterase activity in Alzheimer disease. We previously reported that traditional acetylcholinesterase inhibitors such as BW284C51, tacrine, and physostigmine were more potent inhibitors of the acetylcholinesterase in normal axons and cell bodies than of the acetylcholinesterase in plaques and tangles. We now report that the reverse pattern is seen with indoleamines (such as serotonin and its precursor 5-hydroxytryptophan), carboxypeptidase inhibitor, and the nonspecific protease inhibitor bacitracin. These substances are more potent inhibitors of the cholinesterases in plaques and tangles than of those in normal axons and cell bodies. These results show that the enzymatic properties of plaque and tangle-associated cholinesterases diverge from those of normal axons and cell bodies. The selective susceptibility to bacitracin and carboxypeptidase inhibitor indicates that the catalytic sites of plaque and tangle-bound cholinesterases are more closely associated with peptidase or protease-like properties than the catalytic sites of cholinesterases in normal axons and cell bodies. This shift in enzymatic affinity may lead to the abnormal protein processing that is thought to play a major role in the pathogenesis of Alzheimer disease. The availability of pharmacological and dietary means for altering brain indoleamines raises therapeutic possibilities for inhibiting the abnormal cholinesterase activity associated with Alzheimer disease. Images PMID:8421706

Synthesis, biological evaluation, QSAR study and molecular docking of novel N-(4-amino carbonylpiperazinyl) (thio)phosphoramide derivatives as cholinesterase inhibitors.

Science.gov (United States)

Gholivand, Khodayar; Ebrahimi Valmoozi, Ali Asghar; Bonsaii, Mahyar

2014-06-01

Novel (thio)phosphoramidate derivatives based on piperidincarboxamide with the general formula of (NH2-C(O)-C5H9N)-P(X=O,S)R1R2 (1-5) and (NH2-C(O)-C5H9N)2-P(O)R (6-9) were synthesized and characterized by (31)P, (13)C, (1)H NMR, IR spectroscopy. Furthermore, the crystal structure of compound (NH2-C(O)-C5H9N)2-P(O)(OC6H5) (6) was investigated. The activities of derivatives on cholinesterases (ChE) were determined using a modified Ellman's method. Also the mixed-type mechanisms of these compounds were evaluated by Lineweaver-Burk plots. Molecular docking and quantitative structure-activity relationship (QSAR) were used to understand the relationship between molecular structural features and anti-ChE activity, and to predict the binding affinity of phosphoramido-piperidinecarboxamides (PAPCAs) to ChE receptors. From molecular docking analysis, noncovalent interactions especially hydrogen bonding as well as hydrophobic was found between PAPCAs and ChE. Based on the docking results, appropriate molecular structural parameters were adopted to develop a QSAR model. DFT-QSAR models for ChE enzymes demonstrated the importance of electrophilicity parameter in describing the anti-AChE and anti-BChE activities of the synthesized compounds. The correlation matrix of QSAR models and docking analysis confirmed that electrophilicity descriptor can control the influence of the hydrophobic properties of P=(O, S) and CO functional groups of PAPCA derivatives in the inhibition of human ChE enzymes. Copyright © 2014 Elsevier Inc. All rights reserved.

Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues

International Nuclear Information System (INIS)

Prody, C.A.; Zevin-Sonkin, D.; Gnatt, A.; Goldberg, O.; Soreq, H.

1987-01-01

To study the primary structure and regulation of human cholinesterases, oligodeoxynucleotide probes were prepared according to a consensus peptide sequence present in the active site of both human serum pseudocholinesterase and Torpedo electric organ true acetylcholinesterase. Using these probes, the authors isolated several cDNA clones from λgt10 libraries of fetal brain and liver origins. These include 2.4-kilobase cDNA clones that code for a polypeptide containing a putative signal peptide and the N-terminal, active site, and C-terminal peptides of human BtChoEase, suggesting that they code either for BtChoEase itself or for a very similar but distinct fetal form of cholinesterase. In RNA blots of poly(A) + RNA from the cholinesterase-producing fetal brain and liver, these cDNAs hybridized with a single 2.5-kilobase band. Blot hybridization to human genomic DNA revealed that these fetal BtChoEase cDNA clones hybridize with DNA fragments of the total length of 17.5 kilobases, and signal intensities indicated that these sequences are not present in many copies. Both the cDNA-encoded protein and its nucleotide sequence display striking homology to parallel sequences published for Torpedo AcChoEase. These finding demonstrate extensive homologies between the fetal BtChoEase encoded by these clones and other cholinesterases of various forms and species

Small Quaternary Inhibitors K298 and K524: Cholinesterases Inhibition, Absorption, Brain Distribution, and Toxicity.

Science.gov (United States)

Karasova, Jana Zdarova; Hroch, Milos; Musilek, Kamil; Kuca, Kamil

2016-02-01

Inhibitors of acetylcholinesterase (AChE) may be used in the treatment of various cholinergic deficits, among them being myasthenia gravis (MG). This paper describes the first in vivo data for promising small quaternary inhibitors (K298 and K524): acute toxicity study, cholinesterase inhibition, absorption, and blood-brain barrier penetration. The newly prepared AChE inhibitors (bis-quinolinium and quinolinium compounds) possess a positive charge in the molecule which ensures that anti-AChE action is restricted to peripheral effect. HPLC-MS was used for determination of real plasma and brain concentration in the pharmacokinetic part of the study, and standard non-compartmental analysis was performed. The maximum plasma concentrations were attained at 30 min (K298; 928.76 ± 115.20 ng/ml) and 39 min (K524; 812.40 ± 54.96 ng/ml) after i.m. Both compounds are in fact able to target the central nervous system. It seems that the difference in the CNS distribution profile depends on an active efflux system. The K524 brain concentration was actively decreased to below an effective level; in contrast, K298 progressively accumulated in brain tissue. Peripheral AChE inhibitors are still first-line treatment in the mild forms of MG. Commonly prescribed carbamates have many severe side effects related to AChE carbamylation. The search for new treatment strategies is still important. Unlike carbamates, these new compounds target AChE via apparent π-π or π-cationic interaction aside at the AChE catalytic site.

El humanismo del Che Che's Humanism

Directory of Open Access Journals (Sweden)

Avelino Fernández Espert

2004-08-01

Full Text Available Los autores, estudiosos de la raigal influencia del pensamiento y la obra del Comandante Dr. Ernesto Guevara de la Serna (Che en Cuba y América, proyectan la estampa humanista de este revolucionario médico, con el empleo de las más trascendentes pinceladas históricas de un amplia hoja de vida en distintas latitudes del mundo. El Che, joven estudiante, médico graduado con prometedoras dotes que sabe ubicar al ser humano y sus valores por encima de un promisorio futuro como científico y profesional de la medicina. El artículo dedica atención especial a sus conceptos sobre el hombre, su vida e historia y a su proverbial apego a una ética revolucionaria de elevado calibre. El artículo contribuye al enriquecimiento de los conocimientos sobre el desarrollo histórico del humanismo médico cubano, al proyectarlo en la figura de uno de sus más míticos modelosThe authors, studious of the extraordinary influence of Commandant and Dr. Ernesto Guevara de la Serna 's thought in Cuba and America, unveil the humanist perspective of this revolutionary doctor, through the most transcendental historical events in this man's life in different latitudes of the world. Che, young student, medicine doctor with promising gifts that knew how to place the human being and his values above his promissory future as scientific and medicine professional. The article dedicates special attention to his concepts about men, as well as his life and history and to his proverbial attachment to valuable revolutionary ethics. The article contributes to the enrichment of knowledge on the historical development of Cuban medical humanism, by reflecting this in the figure of one of its most mythical models

Comparative Effects of Oral Chlorpyrifos Exposure on Cholinesterase Activity and Muscarinic Receptor Binding in Neonatal and Adult Rat Heart

Science.gov (United States)

Howard, Marcia D.; Mirajkar, Nikita; Karanth, Subramanya; Pope, Carey N.

2010-01-01

Organophosphorus (OP) pesticides elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for inactivating acetylcholine (ACh) at cholinergic synapses. A number of OP toxicants have also been reported to interact directly with muscarinic receptors, in particular the M2 muscarinic subtype. Parasympathetic innervation to the heart primarily regulates cardiac function by activating M2 receptors in the sinus node, atrial-ventricular node and conducting tissues. Thus, OP insecticides can potentially influence cardiac function in a receptor–mediated manner indirectly by inhibiting acetylcholinesterase and directly by binding to muscarinic M2 receptors. Young animals are generally more sensitive than adults to the acute toxicity of OP insecticides and age related differences in potency of direct binding to muscarinic receptors by some OP toxicants have been reported. We thus compared the effects of the common OP insecticide chlorpyrifos (CPF) on functional signs of toxicity and cardiac ChE activity and muscarinic receptor binding in neonatal and adult rats. Dosages were based on acute lethality (i.e., 0.5 and 1 × LD10: neonates, 7.5 and 15 mg/kg; adults, 68 and 136 mg/kg). Dose- and time-related changes in body weight and cholinergic signs of toxicity (involuntary movements) were noted in both age groups. With 1 × LD10, relatively similar maximal reductions in ChE activity (95%) and muscarinic receptor binding (≈ 30%) were noted, but receptor binding reductions appeared earlier in adults and were more prolonged in neonates. In vitro inhibition studies indicated that ChE in neonatal tissues was markedly more sensitive to inhibition by the active metabolite of chlorpyrifos (i.e., chlorpyrifos oxon, CPO) than enzyme in adult tissues (IC50 values: neonates, 17 nM; adults, 200 nM). Chelation of free calcium with EDTA had relatively little effect on in vitro cholinesterase inhibition, suggesting that differential A-esterase activity was not

Changes of serum pancreatic stone protein and cholinesterase contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage

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Zhi-Hong Ren

2017-10-01

Full Text Available Objective: To study the changes of serum pancreatic stone protein (PSP and cholinesterase (ChE contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage. Methods: A total of 64 children with sepsis who were treated in the hospital between January 2015 and January 2017 were selected as observation group, and 50 healthy children who received vaccination in the hospital during the same period were selected as normal control group. The contents of PSP, ChE, inflammatory factors as well as liver and kidney function indexes in the two groups were detected. Pearson test was used to assess the correlation of serum PSP and ChE contents with systemic inflammatory response and target organ damage in children with sepsis. Results: Serum PSP content of observation group was higher than that of control group while ChE content was lower than that of control group; serum inflammatory factors PCT, CRP, IL-1, IL-6 and IL-10 contents of observation group were higher than those of normal control group; liver function indexes TBIL, ALT and AST contents were higher than those of normal control group; kidney function indexes Scr and BUN contents were higher than those of normal control group. Pearson test showed that the serum PSP and ChE contents in children with sepsis were directly correlated with the systemic inflammatory response as well as liver and renal function injury. Conclusion: Serum PSP content significantly increases while ChE content significantly decreases in children with sepsis and the specific change is directly correlated with the overall disease severity.

Potential anti-cholinesterase and β-site amyloid precursor protein cleaving enzyme 1 inhibitory activities of cornuside and gallotannins from Cornus officinalis fruits.

Science.gov (United States)

Bhakta, Himanshu Kumar; Park, Chan Hum; Yokozawa, Takako; Tanaka, Takashi; Jung, Hyun Ah; Choi, Jae Sue

2017-07-01

Cholinesterase (ChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors are promising agents for the treatment of Alzheimer's disease (AD). In the present study, we examined the inhibitory activity of seven compounds isolated from the fruits of Cornus officinalis, cornuside, polymeric proanthocyanidins, 1,2,3-tri-O-galloyl-β-D-glucose, 1,2,3,6-tetra-O-galloyl-β-D-glucose, tellimagrandin I, tellimagrandin II, and isoterchebin, against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and BACE1. All of the compounds displayed concentration-dependent in vitro inhibitory activity toward the ChEs and BACE1. Among them, tellimagrandin II exhibited the best inhibitory activity toward ChEs, whereas the best BACE1 inhibitor was 1,2,3,6-tetra-O-galloyl-β-D-glucose. Isoterchebin and polymeric proanthocyanidins were also significant ChE inhibitors. The kinetic and docking studies demonstrated that all compounds interacted with both the catalytic active sites and the peripheral anionic sites of the ChEs and BACE1. Tellimagrandin II, isoterchebin, and the polymeric proanthocyanidins exhibited concentration-dependent inhibition of peroxynitrite-mediated protein tyrosine nitration. In conclusion, we identified significant ChE and BACE1 inhibitors from Corni Fructus that could have value as new multi-targeted compounds for anti-AD agents.

Notas sobre el che

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Virginia Bertolotti

2010-06-01

Full Text Available In the present work, I review, in the first place, the bibliography that summarizes the discussion surrounding the etymology of the word che. Then, I analyze the uses of this term in the diachrony as in the synchrony of the Río de la Plata Spanish, which allows me to propose a classification of the uses of the word che in this region. In the third part of the article, I discuss the categorial adscrption of the word che. Finally, the categorial analysis of the diachronic and synchronic empirical evidence allows me to conclude that the vocative uses of the term are a loan from the nominal determinant of the guaraní language, and not a phonic change in the Spanish interjection, thus resolving the etymological issues.

Evaluation of a clinic-based cholinesterase test kit for the Washington State Cholinesterase Monitoring Program.

Science.gov (United States)

Hofmann, Jonathan N; Carden, Angela; Fenske, Richard A; Ruark, Harold E; Keifer, Matthew C

2008-07-01

The Washington State Cholinesterase Monitoring Program for pesticide handlers requires blood draws at local clinics, with samples tested at a central laboratory. At present, workers with inhibited cholinesterase activity may be re-exposed before they can be removed from work. In this study we explored the option of on-site testing at local clinics using the EQM Test-mate Kittrade mark, a portable cholinesterase test kit. Test kit cholinesterase activity measurements were performed on 50 blood samples by our research staff, and compared to measurements on the same samples by the Washington State Public Health Laboratory. Another set of samples was also analyzed with the test kit by medical staff at an eastern Washington clinic. Triplicate measurements with the test kit had a 3.3% average coefficient of variation (CV) for plasma cholinesterase (PChE), and a 3.5% average CV for erythrocyte cholinesterase (AChE) measurements. The kit's PChE measurements were similar to PHL measurements (average ratio of 0.98) when performed in the laboratory, but had a tendency to underestimate activity when used in the clinic setting (average ratio of 0.87). The kit systematically overestimated AChE activity by 42-48% relative to the PHL measurements, regardless of where the samples were analyzed. This easy-to-use test kit appeared to be a viable method for clinic-based PChE measurements, but was less consistent for AChE measurements performed in the clinic. Absolute measurements with the kit need to be evaluated carefully relative to standardized methods. (c) 2008 Wiley-Liss, Inc.

Dicty_cDB: CHE687 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available CH (Link to library) CHE687 (Link to dictyBase) - - - Contig-U16336-1 - (Link to Or...iginal site) CHE687F 622 - - - - - - Show CHE687 Library CH (Link to library) Clone ID CHE687 (Link to dicty...Base) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U16336-1 Original site URL http://dictycdb.b...KFINQCINEIKEELKGDMQKKTVAVQKLTYIQ MLGFDISWASFKIVEVMSCNKFSSKRIGYLAASQSFNEGTDVIVLATHQIRKDFLSSNQS EAYLALNCLSNICT...LGFDISWASFKIVEVMSCNKFSSKRIGYLAASQSFNEGTDVIVLATHQIRKDFLSSNQS EAYLALNCLSNICTTDLARELANDILTLLSTQKTHILKRAITVLYKIF

[Cholinesterases in total blood measured with a semiquantitative technique, and plasma or erythrocyte cholinesterases measured with quantitative techniques].

Science.gov (United States)

Carmona-Fonseca, Jaime

2007-06-01

An equivalence model which allows comparison of blood cholinesterase values, measured by Lovibond (semiquantitative technique), and Michel, EQM, Monotest (erythrocyte and plasma cholinesterases) values measured by quantitative techniques is required. The performance of Lovibond (Edson tintometric and Limperos & Ranta techniques) were compared with quantitative techniques. The experimental design was descriptive, cross-sectional, and prospective. From a working population (18-59 years) in Valle de Aburrá and Near East of Antioquia. 827 representative samples were chosen for their lack of exposure to cholinesterase-inhibiting plaguicides and affiliated to the Social Security System. (1) 827 workers were classified by Lovibond in four categories: 821 values with 75% of cholinesterase activity or greater (categories 75, 87.5 and 100%) and 6 with cholinesterase activity smaller than 75%. (2) With each quantitative method, the mean values of erythrocyte and plasmatic cholinesterase corresponding to the four values obtained with Lovibond were statistically different to each other. (3) The mean values of each quantitative technique increased when increased the tintometric method value. (4) Lovibond classified the low enzymatic erythrocyte activity very poorly (61-73%), but the classification of the low enzymatic plasma activity was almost completely in error (94-96%). The values of erythrocyte or plasma cholinesterase were adequately estimated by both the quantitative techniques of Michel and EQM and by Lovibond, but only when the enzymatic activity is normal. Lovibond, however, had a poor capacity to designate as "low" the values that were low according to the quantitative tests.

Crèche and School

CERN Multimedia

EVE et École

2018-01-01

IMPORTANT DATES Enrolments 2018-2019 Enrolments to the Crèche and School for the school year 2018-2019 will take place on 5, 6 and 7 March 2018 from 10 am to 1 pm at the Crèche and School of the CERN Staff Association. Registration forms will be available from Thursday 1st March 2018. For more information, please visit the website: http://nurseryschool.web.cern.ch/. * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Saturday 3 March 2018 Open Day at Crèche and School of the CERN Staff Association Are you considering enrolling your child to the Crèche and School of the CERN Staff Association? If you work at CERN, then this event is for you: come visit the school and meet the Management on Saturday 3 March 2018 from 10 to 12 am It will be our pleasure to present to you our structure, its projects and premises, and answer any questions you may have. Please sign up for one of the two sessions via Doodle before Wednesd...

A review on cholinesterase inhibitors for Alzheimer's disease.

Science.gov (United States)

Anand, Preet; Singh, Baldev

2013-04-01

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is characterized by the deficits in the cholinergic system and deposition of beta amyloid (Aβ) in the form of neurofibrillary tangles and amyloid plaques. Since the cholinergic system plays an important role in the regulation of learning and memory processes, it has been targetted for the design of anti-Alzheimer's drugs. Cholinesterase inhibitors enhance cholinergic transmission directly by inhibiting the enzyme acetylcholinesterase (AChE) which hydrolyses acetylcholine. Furthermore, it has been also demonstrated that both acetylcholinesterase and butrylcholinesterase (BuChE) play an important role in Aβ-aggregation during the early stages of senile plaque formation. Therefore, AChE and BuChE inhibition have been documented as critical targets for the effective management of AD by an increase in the availability of acetylcholine in the brain regions and decrease in the Aβ deposition. This review discusses the different classes of cholinesterase inhibitors including tacrine, donepezil, rivastigmine, galantamine, xanthostigmine, para-aminobenzoic acid, coumarin, flavonoid, and pyrrolo-isoxazole analogues developed for the treatment of AD.

Che cos’è l’antiziganismo?

Directory of Open Access Journals (Sweden)

Leonardo Piasere

2012-01-01

Full Text Available Abstract – IT Chi è zingaro? Colui che chiamo zingaro, che assegno a questa identità e che costituisco come "altro" dal resto della società. In questo senso, la storia degli zingari si confonde con quella dell'"antiziganismo", un neologismo che denota una pratica antica. Ma si può dire che la comparsa della nuova parola è legata agliodierni intrecci tra politiche multiculturali da un lato e politiche neoliberiste dall’altro?Abstract – FRQui est Tsigane? Celui que je nomme Tsigane, que j'assigne à cette identité et que je constitue en "autre" du reste de la société. Dans ce sens, l'histoire des Tsiganes se confond avec celle de l'"antitsiganisme", un néologisme qui recouvre une pratique ancienne. Mais peut-on dire que l'apparition de ce nouveau mot estliée aux croisements actuels entre les politiques multiculturelles d'une part, et les politiques néolibéralesde l'autre? Abstract – EN Who is Gypsy? The person I call Gypsy, to whom I assign this identity, is that I establish as "other" than the rest of society. In this sense, the history of Gypsies merges with that of "antigypsism", a neologism that denotes an ancient practice. But can it be said that the appearance ofthis new word is linked to the current entanglement between multi-cultural politics on one side and neo-liberalist politics on the other?

Crystallization and preliminary X-ray crystallographic analysis of Thermotoga maritima CheA P3-P4-P5 domains in complex with CheW

International Nuclear Information System (INIS)

Park, SangYoun; Kim, Keon Young; Kim, Sunmin; Crane, Brian R.

2012-01-01

T. maritima CheA P3-P4-P5 domains were crystallized in complex with CheW. Low-resolution diffraction data were collected to ∼8 Å using synchrotron X-ray radiation. The CheA–CheW complex plays a key role in bacterial chemotaxis signal transduction by initiating phosphotransfer to response regulators via coupling to the chemoreceptors. CheA (P3-P4-P5 domains) and CheW from Thermotoga maritima were overexpressed in Escherichia coli and crystallized as a complex at 298 K using ammonium dihydrogen phosphate as a precipitant. X-ray diffraction data were collected to ∼8 Å resolution at 100 K using synchrotron radiation. The crystal belonged to space group I222 or I2 1 2 1 2 1 , with unit-cell parameters a = 184.2, b = 286.4, c = 327.7 Å. The asymmetric unit may contain six to ten CheA–CheW molecules

The oxime pro-2-PAM provides minimal protection against the CNS effects of the nerve agents sarin, cyclosarin, and VX in guinea pigs.

Science.gov (United States)

Shih, Tsung-Ming; Guarisco, John A; Myers, Todd M; Kan, Robert K; McDonough, John H

2011-01-01

This study examined whether pro-2-PAM, a pro-drug dihydropyridine derivative of the oxime 2-pralidoxime (2-PAM) that can penetrate the brain, could prevent or reverse the central toxic effects of three nerve agents; sarin, cyclosarin, and VX. The first experiment tested whether pro-2-PAM could reactivate guinea pig cholinesterase (ChE) in vivo in central and peripheral tissues inhibited by these nerve agents. Pro-2-PAM produced a dose-dependent reactivation of sarin- or VX-inhibited ChE in both peripheral and brain tissues, but with substantially greater reactivation in peripheral tissues compared to brain. Pro-2-PAM produced 9-25% reactivation of cyclosarin-inhibited ChE in blood, heart, and spinal cord, but no reactivation in brain or muscle tissues. In a second experiment, the ability of pro-2-PAM to block or terminate nerve agent-induced electroencephalographic seizure activity was evaluated. Pro-2-PAM was able to block sarin- or VX-induced seizures (16-33%) over a dose range of 24-32 mg/kg, but was ineffective against cyclosarin-induced seizures. Animals that were protected from seizures showed significantly less weight loss and greater behavioral function 24 h after exposure than those animals that were not protected. Additionally, brains were free from neuropathology when pro-2-PAM prevented seizures. In summary, pro-2-PAM provided modest reactivation of sarin- and VX-inhibited ChE in the brain and periphery, which was reflected by a limited ability to block or terminate seizures elicited by these agents. Pro-2-PAM was able to reactivate blood, heart, and spinal cord ChE inhibited by cyclosarin, but was not effective against cyclosarin-induced seizures.

Evaluation of chlorpyrifos toxicity through a 28-day study: Cholinesterase activity, oxidative stress responses, parent compound/metabolite levels, and primary DNA damage in blood and brain tissue of adult male Wistar rats.

Science.gov (United States)

Kopjar, Nevenka; Žunec, Suzana; Mendaš, Gordana; Micek, Vedran; Kašuba, Vilena; Mikolić, Anja; Lovaković, Blanka Tariba; Milić, Mirta; Pavičić, Ivan; Čermak, Ana Marija Marjanović; Pizent, Alica; Lucić Vrdoljak, Ana; Želježić, Davor

2018-01-05

In this 28 day-study, we evaluated the effects of the insecticide chlorpyrifos orally administered to Wistar rats at doses 0.160, 0.015, and 0.010 mg/kg b. w./day. Following treatment, total cholinesterase activity and activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were measured. Oxidative stress responses were evaluated using a battery of endpoints to establish lipid peroxidation, changes in total antioxidant capacity, level of reactive oxygen species (ROS), glutathione (GSH) level and activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase. Using HPLC-UV DAD analysis, levels of the parent compound and its main metabolite 3,5,6-trichloro-2-pyridinol in plasma and brain tissue were measured. The genotoxic effect was estimated using alkaline comet assay in leukocytes and brain tissue. The exposure did not result in significant effects on total cholinesterase, AChE and BChE activity in plasma and brain tissue. Lipid peroxidation slightly increased both in plasma and brain tissue. Total antioxidant capacity, ROS and GSH levels were marginally influenced by the exposure. Treatment led to significant increases of GSH-Px activity in blood, SOD activity in erythrocytes and a slight increase of catalase activity in plasma. HPLC-UV DAD analysis revealed the presence of both the parent compound and its main metabolite in the plasma of all of the experimental animals and brain tissue of the animals treated at the two higher doses. All of the tested doses of chlorpyrifos were slightly genotoxic, both to leukocytes and brain tissue. Our results call for further research using other sensitive biomarkers of effect, along with different exposure scenarios. Copyright © 2017 Elsevier B.V. All rights reserved.

Exposureassessmentof greenhouseworkerswithanti-cholinesterase pesticides by biological monitoring

Directory of Open Access Journals (Sweden)

Sh Bakand

2012-12-01

Full Text Available   Background and Aims: Organophosphate compounds are the most popular insecticides with the widespread application in pest control. These toxic compounds interfere with the blood cholinesterase and inhibit the cholinestarse activity.Measurement of Cholinesterase activity is widely used for diagnosis of poisoning and adverse effects caused by pesticides. Green-house workers are one of the important occupational groups with the high risk of poisoning with organophosphate and karbamat pesticides .The purpose of this study was to assess the exposure of green-house workers with anti-cholinesterase toxic compounds by measuring the blood cholinesterase activity using electrometric method.   Methods: This research is a descriptive cross sectional study that carried out on farmers of the cucumber green-houses . In this study, 40 workers were selected and their blood cholinesterase enzyme activity were measured using electrometric method . In electrometric method the reduction of cholinesterase activity can be measured through recording the changes of blood pH induced by anticholinestrase agents . The results were analyzed by version16 of spss software.   Results: Based on the obtained results the amount of erythrocyte cholinesterase enzyme inhibition was between 1 / 77% to 35 / 4% and the mean and standard deviation was 23 / 2% ±9 / 68.   Similarly, the amount of plasma cholinesterase enzyme inhibition was between 1% to 28% and the mean and standard deviation was equal to 16/57 ±7 / 92.   Following the analysis of results 25% (n=10 of the workers were identified with no poisoning, 17.5% (n = 7 with minor poisoning , 55% (n=22 with moderate poisoning and 2.5% (n=1 with severe poisoning.     Conclusion : Organophosphate poisoning has been reported as the third cause of poisoning and also the leading cause of poisoning deaths in our country.Therefore, considering the results of this research and the importance of the evaluation of workers exposure

CheMentor Software System by H. A. Peoples

Science.gov (United States)

Reid, Brian P.

1997-09-01

CheMentor Software System H. A. Peoples. Computerized Learning Enhancements: http://www.ecis.com/~clehap; email: clehap@ecis.com; 1996 - 1997. CheMentor is a series of software packages for introductory-level chemistry, which includes Practice Items (I), Stoichiometry (I), Calculating Chemical Formulae, and the CheMentor Toolkit. The first three packages provide practice problems for students and various types of help to solve them; the Toolkit includes "calculators" for determining chemical quantities as well as the Practice Items (I) set of problems. The set of software packages is designed so that each individual product acts as a module of a common CheMentor program. As the name CheMentor implies, the software is designed as a "mentor" for students learning introductory chemistry concepts and problems. The typical use of the software would be by individual students (or perhaps small groups) as an adjunct to lectures. CheMentor is a HyperCard application and the modules are HyperCard stacks. The requirements to run the packages include a Macintosh computer with at least 1 MB of RAM, a hard drive with several MB of available space depending upon the packages selected (10 MB were required for all the packages reviewed here), and the Mac operating system 6.0.5 or later.

Che legend elab ka 40 aastat hiljem / Evelyn Kaldoja

Index Scriptorium Estoniae

Kaldoja, Evelyn, 1980-

2007-01-01

Ilmunud ka: Postimees : na russkom jazõke 9. okt. lk. 10. Argentinas sündinud ja 1967. aastal hukatud revolutsionääri Ernesto Che Guevara poliitikukarjäärist, tema panusest Kuuba revolutsiooni ja poliitikasse. Ernesto Che Guevara mälestamisest Ladina-Ameeerika riikides. Lisa: Kuuba revolutsioon; Che Guevara elu

DDE increased the toxicity of parathion to coturnix quail

Science.gov (United States)

Ludke, J.L.

1977-01-01

Adult male Japanese quail (Coturnix coturnix) were exposed to DDE or chlordane in the diet and subsequently dosed with parathion or paraoxon. Pretreatment with 5 or 50 ppm DDE in the diet for 12 weeks resulted in increased cholinesterase (ChE) activity in plasma, but not in the brain. Dietary concentrations of 5 and 50 ppm DDE caused increased susceptibility of quail that were challenged with parathion or paraoxon. The increased mortality resulting from DDE pretreatment was reflected in brain ChE inhibition. The synergistic action of DDE was apparent after 3 days of exposure to 50 ppm DDE and 1 week of exposure to 5 ppm DDE. Birds exposed for 3 weeks to 5 or 50 ppm DDE retained their DDE-potentiated sensitivity to parathion after 2 weeks on clean diet. Chlordane pretreatment resulted in decreased susceptibility (antagonism) to parathion, but not to paraoxon dosage. Implications of differing responses in ChE and mortality among controls, DDE-, and chlordane-pretreated birds after parathion or paraoxon dosage are discussed.

Cholinesterase activities in the scallop Pecten jacobaeus: Characterization and effects of exposure to aquatic contaminants

International Nuclear Information System (INIS)

Stefano, Bonacci; Ilaria, Corsi; Silvano, Focardi

2008-01-01

Nearshore marine environments of industrialized countries are increasingly threatened by anthropogenic pollution. It is therefore a priority task to investigate the sensitivity of new ecotoxicological warning signals of the occurrence and effects of aquatic pollutants. The main aims of the present study were: 1) to characterize the biochemical properties of ChEs in tissues of the bivalve Pecten jacobaeus, using different specific substrates and selective inhibitors; 2) to measure sensitivity of ChE activities to in vitro exposure to the OPs azamethiphos and DFP and to the heavy metals cadmium and zinc. Our final aim was to carry out a preliminary evaluation of the suitability of ChEs measurement in tissues of the scallop for monitoring marine environmental quality and neurotoxic compounds contamination in the Mediterranean Sea. Responses to specific inhibitors have suggested that ChEs in adductor muscle share many characteristics with vertebrate acetylcholinesterase. Dose-dependent inhibition of ChE was observed in response to in vitro exposure to environmental contaminants such as cadmium and azamethiphos. Sensitivity to zinc and DFP was lower. ChEs in P. jacobaeus might therefore have potential as a sensitive biomarker for monitoring marine pollution. Results of the present study will be useful to focus further experiment of exposure to pollutants under in vivo conditions. Capsule: Cholinesterase activities in scallop Pecten jacobaeus were observed to be sensitive to contaminants in vitro and may therefore have potential as biomarkers for monitoring water pollution

Cholinesterase activities in the scallop Pecten jacobaeus: Characterization and effects of exposure to aquatic contaminants

Energy Technology Data Exchange (ETDEWEB)

Stefano, Bonacci [Department of Environmental Sciences ' G. Sarfatti' , University of Siena, Via P.A. Mattioli 4, I-53100 Siena (Italy)], E-mail: bonacci@unisi.it; Ilaria, Corsi [Department of Environmental Sciences ' G. Sarfatti' , University of Siena, Via P.A. Mattioli 4, I-53100 Siena (Italy)], E-mail: corsii@unisi.it; Silvano, Focardi [Department of Environmental Sciences ' G. Sarfatti' , University of Siena, Via P.A. Mattioli 4, I-53100 Siena (Italy)], E-mail: focardi@unisi.it

2008-03-15

Nearshore marine environments of industrialized countries are increasingly threatened by anthropogenic pollution. It is therefore a priority task to investigate the sensitivity of new ecotoxicological warning signals of the occurrence and effects of aquatic pollutants. The main aims of the present study were: 1) to characterize the biochemical properties of ChEs in tissues of the bivalve Pecten jacobaeus, using different specific substrates and selective inhibitors; 2) to measure sensitivity of ChE activities to in vitro exposure to the OPs azamethiphos and DFP and to the heavy metals cadmium and zinc. Our final aim was to carry out a preliminary evaluation of the suitability of ChEs measurement in tissues of the scallop for monitoring marine environmental quality and neurotoxic compounds contamination in the Mediterranean Sea. Responses to specific inhibitors have suggested that ChEs in adductor muscle share many characteristics with vertebrate acetylcholinesterase. Dose-dependent inhibition of ChE was observed in response to in vitro exposure to environmental contaminants such as cadmium and azamethiphos. Sensitivity to zinc and DFP was lower. ChEs in P. jacobaeus might therefore have potential as a sensitive biomarker for monitoring marine pollution. Results of the present study will be useful to focus further experiment of exposure to pollutants under in vivo conditions. Capsule: Cholinesterase activities in scallop Pecten jacobaeus were observed to be sensitive to contaminants in vitro and may therefore have potential as biomarkers for monitoring water pollution.

Crystallization and preliminary X-ray crystallographic analysis of CheW from Thermotoga maritima: a coupling protein of CheA and the chemotaxis receptor

International Nuclear Information System (INIS)

Park, SangYoun; Crane, Brian R.

2011-01-01

CheW from T. maritima has been crystallized (space group P6 3 , unit-cell parameters a = b = 61.265, c = 361.045 Å). Diffraction data have been collected to 3.1 Å resolution using synchrotron X-ray radiation. The CheW protein plays a key role in bacterial chemotaxis signal transduction by coupling CheA to chemotaxis receptors. CheW from Thermotoga maritima has been overexpressed in Escherichia coli and crystallized at 298 K using ammonium sulfate as a salt precipitant. X-ray diffraction data have been collected to 3.10 Å resolution at 100 K using synchrotron radiation. The crystal belonged to space group P6 3 , with unit-cell parameters a = b = 61.265, c = 361.045 Å. The asymmetric unit may contain four to six CheW molecules

Cholinesterase inhibition modulates visual and attentional brain responses in Alzheimer's disease and health

OpenAIRE

Bentley, P.; Driver, J.; Dolan, R. J.

2008-01-01

Visuo-attentional deficits occur early in Alzheimer's disease (AD) and are considered more responsive to pro-cholinergic therapy than characteristic memory disturbances. We hypothesised that neural responses in AD during visuo-attentional processing would be impaired relative to controls, yet partially susceptible to improvement with the cholinesterase inhibitor physostigmine. We studied 16 mild AD patients and 17 age-matched healthy controls, using fMRI-scanning to enable within-subject plac...

Effects on wildlife of ethyl and methyl parathion applied to California rice fields

Science.gov (United States)

Custer, T.W.; Hill, E.F.; Ohlendorf, H.M.

1985-01-01

Selected rice fields on the Sacramento National Wildlife Refuge Complex were aerially sprayed one time during May or June 1982 with either ethyl (0.11 kg Al/ha) or methyl (0.84 kg AI/ha) parathion for control of tadpole shrimp, Triops longicaudatus. No sick or dead vertebrate wildlife were found or adjacent to the treated rice fields after spraying. Specimens of the following birds and mammals were assayed for brain cholinesterase (ChE) activity to determine exposure to either form of parathion; house mouse, Mus musculus; black-tailed jackrabbit, Lepus californicus; mallard, Anas platyrhynchos; ring-necked pheasant, Phasianus colchicus; American coot, Fulica americana; and red-winged blackbird, Agelaius phoeniceus. Both mice and pheasants from methyl parathion-treated fields had overall mean ChE activities that were significantly (P < 0.05) inhibited compared with controls, and 7, 40, 54 and 57% of individual blackbirds, pheasant, mice, and coots, respectively, had inhibited brain ChE activities (i.e., less than -2 SD of control mean). Although no overall species effect was detected for ethyl parathoid treatment, pheasants (43%), coots (33%), and mice (37%) had significantly inhibited brain ChE activities. Neither of the parathion treatment appeared acutely hazardous to wildlife in or adjacent to rice fields, but sufficient information on potential hazards was obtained to warrant caution in use of these chemicals, especially methyl parathion, in rice fields.

Effects of wildlife of ethyl and methyl parathion applied to California USA rice fields

Science.gov (United States)

Custer, T.W.; Hill, E.F.; Ohlendorf, H.M.

1985-01-01

Selected rice fields on the Sacramento National Wildlife Refuge Complex were aerially sprayed one time during May or June 1982 with either ethyl (0.11 kg Al/ha) or methyl (0.84 kg AI/ha) parathion for control of tadpole shrimp, Triops longicaudatus. No sick or dead vertebrate wildlife were found or adjacent to the treated rice fields after spraying. Specimens of the following birds and mammals were assayed for brain cholinesterase (ChE) activity to determine exposure to either form of parathion; house mouse, Mus musculus; black-tailed jackrabbit, Lepus californicus; mallard, Anas platyrhynchos; ring-necked pheasant, Phasianus colchicus; American coot, Fulica americana; and red-winged blackbird, Agelaius phoeniceus. Both mice and pheasants from methyl parathion-treated fields had overall mean ChE activities that were significantly (P < 0.05) inhibited compared with controls, and 7, 40, 54 and 57% of individual blackbirds, pheasant, mice, and coots, respectively, had inhibited brain ChE activities (i.e., less than -2 SD of control mean). Although no overall species effect was detected for ethyl parathoid treatment, pheasants (43%), coots (33%), and mice (37%) had significantly inhibited brain ChE activities. Neither of the parathion treatment appeared acutely hazardous to wildlife in or adjacent to rice fields, but sufficient information on potential hazards was obtained to warrant caution in use of these chemicals, especially methyl parathion, in rice fields.

Crèche and School - Important dates

CERN Multimedia

Staff Association

2018-01-01

Enrolments 2018-2019 Enrolments to the Crèche and School for the school year 2018-2019 will take place on 5, 6 and 7 March 2018 from 10 am to 1 pm at the Crèche and School of the CERN Staff Association. Registration forms will be available from Thursday 1st March 2018. For more information, please visit the website: http://nurseryschool.web.cern.ch/. * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Saturday 3 March 2018 Open Day at Crèche and School of the CERN Staff Association Are you considering enrolling your child to the Crèche and School of the CERN Staff Association? If you work at CERN, then this event is for you: come visit the school and meet the Management on Saturday 3 March 2018 from 10 to 12 am It will be our pleasure to present to you our structure, its projects and premises, and answer any questions you may have. Please sign up for one of the two sessions via Doodle before Friday 2 March 2018: htt...

Cholinesterases and neurotoxicity as highly sensitive biomarkers for an organophosphate insecticide in a freshwater gastropod (Chilina gibbosa) with low sensitivity carboxylesterases.

Science.gov (United States)

Bianco, Karina; Yusseppone, María Soledad; Otero, Sofía; Luquet, Carlos; Ríos de Molina, María Del Carmen; Kristoff, Gisela

2013-11-15

In the Upper Valley of Río Negro and Río Neuquén in Argentina, agriculture represents the second most important economic activity. Azinphos-methyl has been found in water from this region throughout the year at a maximum concentration of 22.48 μg L(-1) during the application period. Toxicological studies on local non-target species have been performed mostly on vertebrates, while mollusks, which could be more sensitive, have not been studied so far. This work aims to characterize cholinesterase (ChE) and carboxilesterase (CE) activities of Chilina gibbosa, a freshwater gastropod native to southern Argentina and Chile. These enzymes, together with neurotoxicity signals, are evaluated herein after as sensitive biomarkers of exposure to azinphos-methyl at environmentally relevant concentrations. Effects of azinphos-methyl on antioxidant defenses: glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione S-transferase (GST) are also studied in order to complete a set of biomarkers with different sensitivity and specificity, to propose C. gibbosa as a sentinel species. The highest specific activity was obtained with acetylthiocholine as substrate, followed by propionylthiocholine (83% in comparison to acetylthiocholine) and butyrylthiocholine (19%).The lowest Km and the highest efficiency for ChE were obtained with acetylthiocholine. Regarding CEs activities, a higher efficiency was obtained with p-nitrophenyl butyrate than with p-nitrophenyl acetate. Eserine produced significant inhibition of ChE activity (81% with 0.001 mM and 98% with 1mM) while iso-OMPA did not produce any significant effect on ChE. Our results show that C. gibbosa ChE is very sensitive to azinphos-methyl (CI50 0.02 μg L(-1)) while CEs are inhibited at higher concentrations (CI50 1,000 μg L(-1)). CEs have been reported to be more sensitive to OPs than ChEs in most of the aquatic invertebrates protecting the organisms from neurotoxic effects. In contrast, C. gibbosa, has ChE

Cholinesterase inhibition modulates visual and attentional brain responses in Alzheimer's disease and health.

Science.gov (United States)

Bentley, Paul; Driver, Jon; Dolan, Ray J

2008-02-01

Visuo-attentional deficits occur early in Alzheimer's disease (AD) and are considered more responsive to pro-cholinergic therapy than characteristic memory disturbances. We hypothesised that neural responses in AD during visuo-attentional processing would be impaired relative to controls, yet partially susceptible to improvement with the cholinesterase inhibitor physostigmine. We studied 16 mild AD patients and 17 age-matched healthy controls, using fMRI-scanning to enable within-subject placebo-controlled comparisons of effects of physostigmine on stimulus- and attention- related brain activations, plus between-group comparisons for these. Subjects viewed face or building stimuli while performing a shallow judgement (colour of image) or a deep judgement (young/old age of depicted face or building). Behaviourally, AD subjects performed slower than controls in both tasks, while physostigmine benefited the patients for the more demanding age-judgement task. Stimulus-selective (face minus building, and vice versa) BOLD signals in precuneus and posterior parahippocampal cortex were attenuated in patients relative to controls, but increased following physostigmine. By contrast, face-selective responses in fusiform cortex were not impaired in AD and showed decreases following physostigmine for both groups. Task-dependent responses in right parietal and prefrontal cortices were diminished in AD but improved following physostigmine. A similar pattern of group and treatment effects was observed in two extrastriate cortical regions that showed physostigmine-induced enhancement of stimulus-selectivity for the deep versus shallow task. Finally, for the healthy group, physostigmine decreased stimulus and task-dependent effects, partly due to an exaggeration of selectivity during the shallow relative to deep task. The differences in brain activations between groups and treatments were not attributable merely to performance (reaction time) differences. Our results demonstrate

Acute toxicity and cholinesterase inhibition of the nematicide ethoprophos in larvae of gar Atractosteus tropicus (Semionotiformes: Lepisosteidae

Directory of Open Access Journals (Sweden)

Freylan Mena Torres

2012-03-01

Full Text Available Biomarkers are a widely applied approach in environmental studies. Analyses of cholinesterase (ChE, glutathione S-transferase (GST and lipid peroxidation (LPO are biomarkers that can provide information regarding early effects of pollutants at different biochemical levels on an organism. The aim of this study was to evaluate the biomarker approach on a Costa Rican native and relevant species. For this, larvae of gar (Atractosteus tropicus were exposed to the organophosphorus nematicide, ethoprophos. Acute (96hr exposure was conducted with pesticide concentrations ranging from 0.1μg/L to 1 500μg/L. The 96hr LC50 calculated was 859.7μg/L. After exposure, three biomarkers (ChE, GST and LPO were analyzed in fish that survived the acute test. The lowest observed effect concentration (LOEC regarding ChE activity inhibition was 50μg/L. This concentration produced a significant inhibition (p0.05 in GST activity and LPO were observed in A. tropicus larvae after exposure to ethoprophos.El proceso de reproducción inducida de Atractosteus tropicus es útil para la acuicultura y la reintroducción en zonas donde las poblaciones silvestres se han reducido considerablemente. En larvas de esta especie se evaluó la toxicidad aguda, así como la respuesta de tres biomarcadores: actividad colinesterasa (ChE, actividad de Glutation S-transferasa (GST y peroxidación de lípidos (LPO. Asimismo, se realizaron exposiciones agudas (96hr a etoprofos (nematicida organofosforado, en donde se utilizaron concentraciones entre 0.1μg/L y 1 500μg/L del nematicida. La concentración letal 50 (LC50 calculada fue de 859.7μg/L; la máxima concentración sin efecto en los organismos (NOEC 10μg/L y la concentración más baja en la cual se observó algún efecto (LOEC 50μg/L. A esa concentración, el efecto observado fue una reducción significativa (p0.05 luego de la exposición de los organismos a etoprofos.

Inhibition of Cholinesterases and Some Pro-Oxidant induced Oxidative Stress in Rats Brain by Two Tomato (Lycopersicon Esculentum) Varieties

Science.gov (United States)

Oboh, G.; Bakare, O.O.; Ademosun, A.O.; Akinyemi, A.J.; Olasehinde, T.A.

2015-01-01

This study sought to investigate the effects of two tomato varieties [Lycopersicon esculentum Mill. var. esculentum (ESC) and Lycopersicon esculentum Mill. var. cerasiforme (CER)] on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities in vitro. Phenolics content, carotenoids characterisation, inhibition of Fe2+ and quinolinic acid-induced malondialdehyde (MDA) production in rats brain homogenate and NO* scavenging abilities were also assesed in addition to the AChE and BChE inhibition assays. There was no significant difference in the AChE inhibitory ability of the samples, while CER had significantly higher BChE inhibitory activity. Furthermore, the tomatoes inhibited Fe2+ and quinolinic acid-induced MDA production and further exhibited antioxidant activities through their NO* scavenging abilities. There was no significant difference in the phenolic content of the samples, while significantly high amounts of lycopene were detected in the tomatoes. The cholinesterase-inhibition and antioxidant properties of the “tomatoes” could make them good dietary means for the management of neurodegenerative disorders.

Evaluation the protective effect of diphenhydramine against acute toxicity induced by levamisole in male mice

Directory of Open Access Journals (Sweden)

M.Y. Matti

2015-06-01

Full Text Available The aim of this study was to evaluate the protective effect of different doses of diphenhydramine against acute toxicosis with Levamisole. The Mechanism of levamisole induced acute toxicity and that of protective effect of diphenhydramine against Levamisole toxicosis also examined on the level of cholinesterase (ChE activity. Subcutanous injection of 100mg/kg levamisole in male mice with induced cholinergic over stimulation and death in 100% of animals. The Toxicosis was not related to the significantly decreased in plasma, red blood cells and brain ChE activity. Injection low dose of diphenhydramin 2.5mg/kg S.C. 15 min before levamisole produced protective effect against acute toxicity with levamisole. Significantly decreased the severity of toxicosis and increased survival rates to 100%. Diphenhydramine at low dose alone or with acute dose of levamisole did not Produced Significantly inhibition in ChE activity.The data suggested that the toxic effect of Levamisole was not related to inhibition of ChE. The low dose of diphenhydramine protected mice from Levamisole toxicity. The antidoatal effect of diphenhydramine not at the level of protection from ChE inhibition. There was no adverse interaction between two drugs.

Heterozygous Che-1 KO mice show deficiencies in object recognition memory persistence.

Science.gov (United States)

Zalcman, Gisela; Corbi, Nicoletta; Di Certo, Maria Grazia; Mattei, Elisabetta; Federman, Noel; Romano, Arturo

2016-10-06

Transcriptional regulation is a key process in the formation of long-term memories. Che-1 is a protein involved in the regulation of gene transcription that has recently been proved to bind the transcription factor NF-κB, which is known to be involved in many memory-related molecular events. This evidence prompted us to investigate the putative role of Che-1 in memory processes. For this study we newly generated a line of Che-1(+/-) heterozygous mice. Che-1 homozygous KO mouse is lethal during development, but Che-1(+/-) heterozygous mouse is normal in its general anatomical and physiological characteristics. We analyzed the behavioral characteristic and memory performance of Che-1(+/-) mice in two NF-κB dependent types of memory. We found that Che-1(+/-) mice show similar locomotor activity and thigmotactic behavior than wild type (WT) mice in an open field. In a similar way, no differences were found in anxiety-like behavior between Che-1(+/-) and WT mice in an elevated plus maze as well as in fear response in a contextual fear conditioning (CFC) and object exploration in a novel object recognition (NOR) task. No differences were found between WT and Che-1(+/-) mice performance in CFC training and when tested at 24h or 7days after training. Similar performance was found between groups in NOR task, both in training and 24h testing performance. However, we found that object recognition memory persistence at 7days was impaired in Che-1(+/-) heterozygous mice. This is the first evidence showing that Che-1 is involved in memory processes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Pharmacological properties of donepezil hydrochloride (Aricept), a drug for Alzheimer's disease].

Science.gov (United States)

Ogura, H; Kosasa, T; Araki, S; Yamanishi, Y

2000-01-01

One of the most consistent changes associated with Alzheimer's disease (AD) is a deficit in central cholinergic neurotransmission. Donepezil hydrochloride (DPZ), a novel class of cholinesterase (ChE) inhibitors, inhibits degradation of acetylcholine (ACh) and activates central cholinergic system. In in vitro studies, DPZ more selectively inhibited acetylcholinesterase (IC50: 6.7 nM) than butyrylcholinesterase (IC50: 7400 nM), while tacrine inhibited both acetylcholinesterase (IC50: 77 nM) and butyrylcholinesterase (IC50: 69 nM). After oral dosing, DPZ (ID50: 2.6 mg/kg) inhibited brain ChE dose-dependently without any remarkable effect on ChE in the heart and small intestine, whereas tacrine (ID50: 9.5 mg/kg) inhibited ChE equally in the brain and peripheral tissues. Brain microdialysis revealed that DPZ (2.5 mg/kg) enhanced extracellular ACh concentrations in the cerebral cortex and hippocampus in rats. In behavioral studies, DPZ counteracted both the deficit in passive avoidance induced by lesioning of the nucleus basalis magnocellularis (0.125-1.0 mg/kg) and the impairment in acquisition of a hidden-platform water maze task after lesioning of the medial septum in rats (0.5 mg/kg). DPZ also inhibited the scopolamine-induced impairment of radial maze performance (0.5 mg/kg). Placebo-controlled clinical studies of 12- and 24-week treatments of DPZ (5 mg, 10 mg/day) clearly showed an improvement in cognitive scores of probable AD patients.

Changes of serum levels of prealbumin (PAB), cholinesterase (CHE), total bile acid (TBA) and ALT as related to the severity of inflammatory process and hepatic fibrosis in patients with chronic virus B hepatitis

International Nuclear Information System (INIS)

Chi Xiaoxia; Chen Jianxiong; Xiong Ying

2005-01-01

Objective: To study the correlationship between the serum levels of PAB, CHE, TBA, ALT and the severity of the disease process in patients with chronic virus B hepatitis. Methods: Serum levels of PAB, CHE, ALT (with biochemical methods) and TBA (with RIA) were examined in 93 patients with biopsy proven virus B hepatitis and 46 controls. Results: The 93 patients were of two groups: a less advanced group (n=51) and a more advanced group (n=42). Serum TBA, ALT levels were significnatly higher and serum PAB, CHE levels were significantly lower in the more advanced group than those in the less advanced group (P 0 to s 4 . Changes of levels of ALT were of no regular pattern, but serum levels of TBA regularly increased and levels of PAB, CHE regularly decreased as the fibrosis grading proceeded from s 0 to s 4 and the differences between the levels in s 4 and any other grading were significant (P<0.01). Conclusion: Combined determination of these serum markers might reflect the degree of inflammatory process and hepatic fibrosis in patients with virus B hepatitis, leading to earlier detection of cirrhosis. (authors)

l'italiano che cambia: apocalisse o palingenesi? alcune riflessioni ...

African Journals Online (AJOL)

User

idea that a real linguistic apocalypse is to be found on one hand, in what. Calvino ... nell'italiano contemporaneo da una prospettiva che, audacemente, definiamo ...... 'terrore semantico', cioè la fuga di fronte a ogni vocabolo che abbia di.

Protection against soman and sarin exposure by transdermal physostigmine and scopolamine

Energy Technology Data Exchange (ETDEWEB)

Meshulam, Y.; Davidovici, R.; Levy, A.

1993-05-13

The purpose of this study was to evaluate the prophylactic efficacy of physostigmine (physo), administered via sustained release (SR) methods, with and without scopolamine, against soman and sarin exposure in guinea-pigs. Transdermal physo pad (3 sq cm/kg; 60-80 ug/sq cm), containing a vehicle based on propionic acid, was applied onto the dorsal back of the animals, 24 hours before exposure to the cholinesterase (ChE) inhibitors. At the time of exposure, physo concentrations in brain and plasma were 3.6 ng/g and 4.1 ng/ml respectively. Brain and whole blood ChE activity were inhibited to 70% and 57% of their original activity. Transdermal physo by itself protected up to 70% of the animals exposed to 1.5 LD(50) of soman or sarin (100% mortality was recorded in the control group). Combining transdermal physo with Scopoderm (by Ciba Geigy Inc.) provided full protection against 1.5 LD(50).

Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of cholinesterase inhibitors.

Science.gov (United States)

Botić, Tanja; Defant, Andrea; Zanini, Pietro; Žužek, Monika Cecilija; Frangež, Robert; Janussen, Dorte; Kersken, Daniel; Knez, Željko; Mancini, Ines; Sepčić, Kristina

2017-08-18

The brominated pyrroloiminoquinone alkaloids discorhabdins B, L and G and 3-dihydro-7,8- dehydrodiscorhabdin C, isolated from methanol extracts of two specimens of Latrunculia sp. sponges collected near the Antarctic Peninsula, are here demonstrated for the first time to be reversible competitive inhibitors of cholinesterases. They showed K i for electric eel acetylcholinesterase of 1.6-15.0 μM, for recombinant human acetylcholinesterase of 22.8-98.0 μM, and for horse serum butyrylcholinesterase of 5.0-76.0 μM. These values are promising when compared to the current cholinesterase inhibitors used for treatment of patients with Alzheimer's disease, to counteract the acetylcholine deficiency in the brain. Good correlation was obtained between IC 50 data and results by molecular docking calculation on the binding interactions within the acetylcholinesterase active site, which also indicated the moieties in discorhabdin structures involved. To avoid unwanted peripheral side effects that can appear in patients using some acetylcholinesterase inhibitors, electrophysiological experiments were carried out on one of the most active of these compounds, discorhabdin G, which confirmed that it had no detectable undesirable effects on neuromuscular transmission and skeletal muscle function. These findings are promising for development of cholinesterase inhibitors based on the scaffold of discorhabdins, as potential new agents for treatment of patients with Alzheimer's disease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Discovering Che-1/AATF: a new attractive target for cancer therapy

Directory of Open Access Journals (Sweden)

Simona eIezzi

2015-04-01

Full Text Available The transcriptional cofactor Che-1/AATF is currently emerging as an important component of the DNA damage response machinery, the complex signaling network that maintains genome integrity and prevents tumorigenesis. Moreover this protein is involved in a wide range of cellular pathways, regulating proliferation and survival in both physiological and pathological conditions. Notably, some evidence indicates that dysregulation of Che-1/AATF levels are associated with the transformation process and elevated levels of Che-1/AATF are required for tumor cell survival. It is for these reasons that Che-1/AATF has been regarded as an attractive, still theoretical, therapeutic target for cancer treatments. In this review, we will provide an updated overview of Che-1/AATF activities, from transcriptional regulation to DNA damage response.

Cholinesterase inhibitors and hospitalization for bradycardia: a population-based study.

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Laura Y Park-Wyllie

2009-09-01

Full Text Available BACKGROUND: Cholinesterase inhibitors are commonly used to treat dementia. These drugs enhance the effects of acetylcholine, and reports suggest they may precipitate bradycardia in some patients. We aimed to examine the association between use of cholinesterase inhibitors and hospitalization for bradycardia. METHODS AND FINDINGS: We examined the health care records of more than 1.4 million older adults using a case-time-control design, allowing each individual to serve as his or her own control. Case patients were residents of Ontario, Canada, aged 67 y or older hospitalized for bradycardia between January 1, 2003 and March 31, 2008. Control patients (3:1 were not hospitalized for bradycardia, and were matched to the corresponding case on age, sex, and a disease risk index. All patients had received cholinesterase inhibitor therapy in the 9 mo preceding the index hospitalization. We identified 1,009 community-dwelling older persons hospitalized for bradycardia within 9 mo of using a cholinesterase inhibitor. Of these, 161 cases informed the matched analysis of discordant pairs. Of these, 17 (11% required a pacemaker during hospitalization, and six (4% died prior to discharge. After adjusting for temporal changes in drug utilization, hospitalization for bradycardia was associated with recent initiation of a cholinesterase inhibitor (adjusted odds ratio [OR] 2.13, 95% confidence interval [CI] 1.29-3.51. The risk was similar among individuals with pre-existing cardiac disease (adjusted OR 2.25, 95% CI 1.18-4.28 and those receiving negative chronotropic drugs (adjusted OR 2.34, 95% CI 1.16-4.71. We found no such association when we replicated the analysis using proton pump inhibitors as a neutral exposure. Despite hospitalization for bradycardia, more than half of the patients (78 of 138 cases [57%] who survived to discharge subsequently resumed cholinesterase inhibitor therapy. CONCLUSIONS: Among older patients, initiation of cholinesterase

Che-1 gene silencing induces osteosarcoma cell apoptosis by inhibiting mutant p53 expression

Energy Technology Data Exchange (ETDEWEB)

Liu, Ming; Wang, Dan, E-mail: danwangwdd@163.com; Li, Ning

2016-04-22

The transcriptional cofactor Che-1 is an RNA polymerase II (Pol II) which is involved in tumorigenesis, such as breast cancer and multiple myeloma. Che-1 can also regulate mutant p53 expression, which plays roles in many types of cancer. In this study, we aimed to investigate the effects and specific mechanism of Che-1 in the regulation of osteosarcoma (OS) cell growth. We found that Che-1 is highly expressed in several kinds of OS cells compared with osteoblast hFOB1.19 cells. MTT and flow cytometry assays showed that Che-1 depletion by siRNA markedly suppressed MG-63 and U2OS cell proliferation and promoted apoptosis. The chromatin immunoprecipitation (ChIP) assay verified the presence of Che-1 on the p53 promoter in MG-63 and U2OS cells carrying mutant p53. Further studies showed that Che-1 depletion inhibited mutant p53 expression. Notably, our study showed that the loss of Che-1 inhibits proliferation and promotes apoptosis in MG-63 cells by decreasing the level of mutant p53. Therefore, these findings open the possibility that silencing of Che-1 will have therapeutic benefit in OS. - Highlights: • Che-1 is highly expressed in several kinds of OS cells. • Che-1 depletion suppressed MG-63 and U2OS cell growth. • Che-1 is existed in the p53 promoter in MG-63 and U2OS cells. • Che-1 depletion inhibited mutant p53 expression. • Che-1 depletion inhibits cell growth by decreasing the level of mutant p53.

Histochemical localization of cholinesterase activity in the dental epithelium of guinea pig teeth.

Science.gov (United States)

Jayawardena, C K; Takano, Y

2004-07-01

Cholinesterase is known for its remarkable diversity in distribution and function. An association of this enzyme with proliferative and morpho-differentiating tissues has been reported in several species. Here we report on the first evidence of the presence of cholinesterase in the enamel organ of continuously erupting incisors and molars of the guinea pig. Frozen sections of the incisors and molars of the guinea pig were incubated for histochemical demonstration of cholinesterase activity by means of the thiocholine method as described by Karnovsky and Root. The cholinesterase activity was observed in several types of cells of the dental epithelium; cells forming the basal portion of the enamel organ, outer enamel epithelium and maturation stage ameloblasts of both the incisors and molars. In the crown analogue side, the outer enamel epithelial cells gained strong reactions for cholinesterase and maintained the reaction throughout the secretory and maturation stages of amelogenesis. In contrast, cholinesterase reactions were lacking in the inner enamel epithelium, pre-ameloblasts, and secretory ameloblasts. In the early stage of enamel maturation, ameloblasts began to show positive reactions for cholinesterase, which was upregulated in the incisal direction. Although both tooth types showed similar reactive patterns for cholinesterase at the growing ends, maturation ameloblasts depicted a different pattern of staining displaying the reactions only sporadically in molars. These data indicate the role of cholinesterase in the enamel organ in tooth morphogenesis and function of guinea pig teeth. Copyright 2004 Springer-Verlag

Pulmonary Toxicity of Cholinesterase Inhibitors

National Research Council Canada - National Science Library

Hilmas, Corey; Adler, Michael; Baskin, Steven I; Gupta, Ramesh C

2006-01-01

.... Whereas nerve agents were produced primarily for military deployment, other cholinesterase inhibitors were used for treating conditions such as myasthenia gravis and as pretreaunents for nerve agent exposure...

Study of Serum Amylase and Serum Cholinesterase in Organophosphorus Poisoning

Directory of Open Access Journals (Sweden)

Sharan Badiger

2016-04-01

Full Text Available Background: Poisoning due to organophosphorus compounds is most commonly seen. Earlier plasma cholinesterase level was used to assess the severity of poisoning. Presently serum amylase is being recommended as a better indicator of severity. Aims and Objectives: To study plasma cholinesterase and serum amylase levels in acute organophosphorus and to correlate serum amylase levels with clinical severity and outcome. Material and Methods: A total of 80 patients in the study admitted to a tertiary care centre within 24 hours with a history of organophosphorus poisoning were included in study. Estimation of plasma cholinesterase and serum rd amylase was done at the time of admission, and on 3 th day and on 5 day. Results: Occurrence of organophosphorus poisoning was more common among age group 21-30 years and among males (57.5%. They were 25 (31.2% farmers, 23 (28.8% st u d e n ts, a n d 2 2 ( 2 7 . 5% h o u s ewi v e s. Monocrotophos (45.0% was commonly used compound. Mean value of plasma cholinesterase and serum amylase at admission are 3693 U/L, and 185.4 U/L. There was significant inhibition of plasma cholinesterase and elevation of serum amylase at th admission with return to normal values on 5 day. Conclusion: Plasma cholinesterase inhibition 200 U/L has been associated with poor prognosis and proneness to respiratory failure.

Exposure of nonbreeding migratory shorebirds to cholinesterase-inhibiting contaminants in the western hemisphere

Science.gov (United States)

Strum, K.M.; Hooper, M.J.; Johnson, K.A.; Lanctot, Richard B.; Zaccagnini, M.E.; Sandercock, B.K.

2010-01-01

Migratory shorebirds frequently forage and roost in agricultural habitats, where they may be exposed to cholinesterase-inhibiting pesticides. Exposure to organophosphorus and carbamate compounds, common anti-cholinesterases, can cause sublethal effects, even death. To evaluate exposure of migratory shorebirds to organophosphorus and carbamates, we sampled birds stopping over during migration in North America and wintering in South America. We compared plasma cholinesterase activities and body masses of individuals captured at sites with no known sources of organophosphorus or carbamates to those captured in agricultural areas where agrochemicals were recommended for control of crop pests. In South America, plasma acetylcholinesterase and butyrylcholinesterase activity in Buff-breasted Sandpipers was lower at agricultural sites than at reference sites, indicating exposure to organophosphorus and carbamates. Results of plasma cholinesterase reactivation assays and foot-wash analyses were inconclusive. A meta-analysis of six species revealed no widespread effect of agricultural chemicals on cholinesterase activity. however, four of six species were negative for acetylcholinesterase and one of six for butyrylcholinesterase, indicating negative effects of pesticides on cholinesterase activity in a subset of shorebirds. Exposure to cholinesterase inhibitors can decrease body mass, but comparisons between treatments and hemispheres suggest that agrochemicals did not affect migratory shorebirds' body mass. Our study, one of the first to estimate of shorebirds' exposure to cholinesterase-inhibiting pesticides, suggests that shorebirds are being exposed to cholinesterase- inhibiting pesticides at specific sites in the winter range but not at migratory stopover sites. future research should examine potential behavioral effects of exposure and identify other potential sitesand levels of exposure. ?? The Cooper Ornithological Society 2010.

Synthesis, cytotoxicity and molecular modelling studies of new phenylcinnamide derivatives as potent inhibitors of cholinesterases.

Science.gov (United States)

Saeed, Aamer; Mahesar, Parvez Ali; Zaib, Sumera; Khan, Muhammad Siraj; Matin, Abdul; Shahid, Mohammad; Iqbal, Jamshed

2014-05-06

The present study reports the synthesis of cinnamide derivatives and their biological activity as inhibitors of both cholinesterases and anticancer agents. Controlled inhibition of brain acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) may slow neurodegeneration in Alzheimer's diseases (AD). The anticholinesterase activity of phenylcinnamide derivatives was determined against Electric Eel acetylcholinesterase (EeAChE) and horse serum butyrylcholinesterase (hBChE) and some of the compounds appeared as moderately potent inhibitors of EeAChE and hBChE. The compound 3-(2-(Benzyloxy)phenyl)-N-(3,4,5-trimethoxyphenyl)acrylamide (3i) showed maximum activity against EeAChE with an IC50 0.29 ± 0.21 μM whereas 3-(2-chloro-6-nitrophenyl)-N-(3,4,5-trimethoxyphenyl)acrylamide (3k) was proved to be the most potent inhibitor of hBChE having IC50 1.18 ± 1.31 μM. To better understand the enzyme-inhibitor interaction of the most active compounds toward cholinesterases, molecular modelling studies were carried out on high-resolution crystallographic structures. The anticancer effects of synthesized compounds were also evaluated against cancer cell line (lung carcinoma). The compounds may be useful leads for the design of a new class of anticancer drugs for the treatment of cancer and cholinesterase inhibitors for Alzheimer's disease (AD). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Perché io credo in colui che ha fatto il mondo

CERN Document Server

Zichichi, Antonino

1999-01-01

Fin troppo spesso si sente dire che il mondo della scienza e quello della religione sono in completa opposizione e che non condividono alcuna esperienza o caratteristica in comune. Nulla potrebbe essere più falso di queste affermazioni secondo Antonino Zichichi, che in quest'opera afferma come la ricerca scientifica e l'esperienza religiosa abbiano in comune molto più di quanto si possa pensare.

Che Guevara

DEFF Research Database (Denmark)

Cristoffanini, Pablo Rolando

2014-01-01

made Che Guevara a political, religious and cultural icon and an object of consumption, despite his total political and military failure in Bolivia and his violent death. Finally the article contrasts the meanings of his image in the original context with new research that calls into question...... with the achievements and connotations of the Cuban Revolution in the context of the Cold War. The current meanings of the image must be read in the context of the global consumer culture. The article analyzes and explains how a conjunction of factors such as communication strategies and the connotations of his image...

Cholinesterase Enzymes Inhibitors from the Leaves of Rauvolfia Reflexa and Their Molecular Docking Study

Directory of Open Access Journals (Sweden)

Vikneswaran Murugaiyah

2013-03-01

Full Text Available Plants of the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders. Rauvolfia reflexa, a member of the family, has been used as an antidote for poisons and to treat malaria. The dichloromethane, ethanol and methanol extracts from the leaves of Rauvolfia reflexa showed potential acetylcholinesterase (AChE and butyrylcholinesterase (BChE inhibitory activities, with IC50 values in the 8.49 to 52.23 g/mL range. Further cholinesterase inhibitory-guided isolation of these extracts afforded four bioactive compounds, namely: (E-3-(3,4,5-trimethoxyphenylacrylic acid (1, (E-methyl 3-(4-hydroxy-3,5-dimethoxyphenyl acrylate (2, 17-methoxycarbonyl-14-heptadecaenyl-4-hydroxy-3-methoxycinnamate (3 and 1,2,3,4-tetrahydro-1-oxo-β-carboline (4. The isolated compounds showed moderate cholinesterase inhibitory activity compared to the reference standard, physostigmine. Compounds 1 and 2 showed the highest inhibitory activity against AChE (IC50 = 60.17 µM and BChE (IC50 = 61.72 µM, respectively. Despite having similar molecular weight, compounds 1 and 2 were structurally different according to their chemical substitution patterns, leading to their different enzyme inhibition selectivity. Compound 2 was more selective against BChE, whereas compound 1 was a selective inhibitor of AChE. Molecular docking revealed that both compounds 1 and 2 were inserted, but not deeply into the active site of the cholinesterase enzymes.

Cholinesterase enzymes inhibitors from the leaves of Rauvolfia reflexa and their molecular docking study.

Science.gov (United States)

Fadaeinasab, Mehran; Hadi, A Hamid A; Kia, Yalda; Basiri, Alireza; Murugaiyah, Vikneswaran

2013-03-25

Plants of the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders. Rauvolfia reflexa, a member of the family, has been used as an antidote for poisons and to treat malaria. The dichloromethane, ethanol and methanol extracts from the leaves of Rauvolfia reflexa showed potential acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, with IC50 values in the 8.49 to 52.23 g/mL range. Further cholinesterase inhibitory-guided isolation of these extracts afforded four bioactive compounds, namely: (E)-3-(3,4,5-trimethoxyphenyl)acrylic acid (1), (E)-methyl 3-(4-hydroxy-3,5-dimethoxyphenyl) acrylate (2), 17-methoxycarbonyl-14-heptadecaenyl-4-hydroxy-3-methoxycinnamate (3) and 1,2,3,4-tetrahydro-1-oxo-β-carboline (4). The isolated compounds showed moderate cholinesterase inhibitory activity compared to the reference standard, physostigmine. Compounds 1 and 2 showed the highest inhibitory activity against AChE (IC50 = 60.17 µM) and BChE (IC50 = 61.72 µM), respectively. Despite having similar molecular weight, compounds 1 and 2 were structurally different according to their chemical substitution patterns, leading to their different enzyme inhibition selectivity. Compound 2 was more selective against BChE, whereas compound 1 was a selective inhibitor of AChE. Molecular docking revealed that both compounds 1 and 2 were inserted, but not deeply into the active site of the cholinesterase enzymes.

Plasma cholinesterase activity of rats, western grey kangaroos, alpacas, sheep, cattle, and horses.

Science.gov (United States)

Mayberry, Chris; Mawson, Peter; Maloney, Shane K

2015-01-01

Plasma cholinesterase activity levels of various species may be of interest to toxicologists or pathologists working with chemicals that interfere with the activity of plasma cholinesterase. We used a pH titration method to measure the plasma cholinesterase activity of six mammalian species. Plasma cholinesterase activity varied up to 50-fold between species: sheep (88 ± 45 nM acetylcholine degraded per ml of test plasma per minute), cattle (94 ± 35), western grey kangaroos (126 ± 92), alpaca (364 ± 70), rats (390 ± 118) and horses (4539 ± 721). We present a simple, effective technique for the assay of plasma cholinesterase activity levels from a range of species. Although labour-intensive, it requires only basic laboratory equipment. Copyright © 2015 Elsevier Inc. All rights reserved.

A crèche on the Meyrin CERN site

CERN Multimedia

Association du personnel

2013-01-01

A few months ago (see Echo 175) we announced the opening, at the end of August, of a crèche at the CERN Staff Association’s nursery school. After a very active summer, where a new floor was added to the canteen building, the new school year started in excellent conditions and, as expected, the new crèche opened on Tuesday 27 August. This crèche, with 13 full-time equivalent places, can accept 18 children aged between three months and two years in a space fully refitted to care for the little ones. A specially designed space for breastfeeding helps mothers working on the site to respect their baby's rhythm. In compliance with the standards of supervision in the canton of Geneva six educators take care of the children in shifts. This new space is fully integrated in the nursery school so that now the crèche, Kindergarten and school of the CERN Staff Association can welcome children aged from three months to six years, from Monday to Friday, and...

Native and tabun-inhibited cholinesterase interactions with oximes

International Nuclear Information System (INIS)

Kovarik, Z.; Katalinic, M.; Sinko, G.

2009-01-01

The phosphorylation of the serine hydroxyl group in the active site of acetylcholinesterase (AChE) inactivates this essential enzyme in neurotransmission. Its related enzyme butyrylcholinesterase (BChE) also interacts with organophosphorus compounds (OP) scavenging anti-cholinesterase agents and protects synaptic AChE from inhibition. Oximes are reactivators of AChE phosphorylated by OP including insecticides and nerve agents. The effectiveness of oxime-assisted reactivation is primarily attributed to the nucleophilic displacement rate of organophosphate, but efficiency varies with the structure of the bound organophosphate, the structure of the oxime as well as rates of several other cholinesterase's reactions. Besides reactivating cholinesterases, oximes also reversibly inhibit both cholinesterases and protect them from phosphorylation by OP. We tested oximes varying in the type of ring (pyridinium and/or imidazolium), the length and type of the linker between rings, and in the position of the oxime group on the ring to find more effective oximes to reactivate tabun-inhibited human erythrocyte AChE and plasma BChE. Herein we bring an overview of in vitro interactions of native and tabun-inhibited AChE and BChE with oximes together with conformational analysis of the oximes relating molecular properties to their reactivation potency.(author)

Award ceremony for the "Crèche and School" competition

CERN Multimedia

Staff Association

2018-01-01

Whenever there is a competition, there are obviously participants – and especially winners! The awards ceremony for the competition to find a new name for the CERN Staff Association's Crèche and School took place on 15 May. During the ceremony, jointly led by Céline Grobon (President of the Crèche and School Steering Committee), Carole Dargagnon (Headmistress of the Crèche and School) and Jean-Baptiste Zenner (Staff Association delegate), the proposals selected by the jury were rewarded. The first place went to Marie-Luz Cavagna for her proposal "Le jardin des petits chercheurs", and the second place to Sarah Palluel for her proposal "Le Jardin des Zélectrons". Finally, Aude Mourey and Sandra Fleury tied for third place with their respective proposals "Les petits atomes" and "La crèche des particules". Can we find the winning name of the competition among...

Los marcadores che y boludo: ¿un caso de rivalidad conversacional?

Directory of Open Access Journals (Sweden)

Markéta Šmídová

2016-11-01

Full Text Available It has been recently suggested that the Argentinian conversational marker che is being replaced by another typical expression, boludo. The purpose of the present paper is to provide a pilot comparative study of these two Argentinian markers in order to examine their free interchangeability and to refute it eventually. A commutation test has been used as a basic tool to compare the behavior and functions of che and boludo and the results have helped to reveal contexts in which it would be inadmissible or inappropriate to employ boludo instead of che due to the possible violation of politeness norms. In the article, che and boludo are considered mainly from the sociolinguistic and pragmatic approaches although some important cultural phenomena are discussed as well.

Effects of two oxadiazolidinones on cholinesterases and acetylcholine receptors

International Nuclear Information System (INIS)

Bakry, N.; Lockyer, S.; Sherby, S.; Eldefrawi, A.; Eldefrawi, M.

1986-01-01

Inhibition of acetylcholinesterase (AChE) and butyryl cholinesterase (BuChE) by 3-(2,3-dihydro-2,2-dimethyl-benzofuran-'7-yl)-5-methoxy-1,3,4-oxadiazol-2( 3 H)-one (DBOX) and 3-(2-methoxyphenyl)-5-methoxy-1,3,4-oxadiazol-2( 3 H)-one (MPOX) was measured by the Ellmann spectrophotometric method. Inhibition was quasi first order and irreversible. DBOX was 2-3 orders of magnitude more potent than MPOX. Housefly brain AChE and horse serum BuChE were more sensitive than AChEs of red blood cells or eel and Torpedo electric organs. It is suggested that the nonesteratic oxadiazolidinones are activated to carbanillates on the surface of the enzyme and produce a carbanillated enzyme which ages rapidly. Carbamate anticholinesterases protected AChE against carbanillation as they did against phosphorylation. At higher concentrations, the two oxadiazolidinones also affected binding of [ 125 I] α bungarotoxin and [ 3 H]perhydrohistrionicotoxin to Torpedo nicotinic acetylcholine receptors, but did not affect binding of [ 3 H]quinuclidinyl benzilate to rat brain muscarinic receptors

Characterization of cholinesterases present in brain and muscle tissues of juvenile blue shark (Prionace glauca

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Luís Miguel Fonseca Alves

2014-06-01

Regarding the in vitro exposure to chlorpyrifos-oxon, we have observed a dose-response pattern showing higher ChE inhibitions with increasing pesticide concentrations and with more than 90% inhibition in the highest concentrations, which reveals the potential of this biomarker for biomonitoring studies and contaminant effect assessment in the blue shark.

I sei numeri dell'universo le forze profonde che spiegano il cosmo

CERN Document Server

Rees, Martin

2002-01-01

È possibile che sei semplici numeri, sei costanti universali, diano conto dell'infinita varietà e della stupefacente complessità del cosmo? L'astrofisico Martin Rees ci mostra che non soltano ciò è possibile, ma in quei sei numeri sono scritti la storia, la struttura e il futuro dell'universo, e che perfino la comparsa della vita sulla terra, e dunque la nostra stessa esistenza, non sarebbe concepibile se uno solo di quei valori numerici, definiti nell'istante che segnò la nascita del mondo, fosse differente. I sei numeri dell'universo ci introducono così ad alcune delle questioni più profonde su cui si interroga oggi la scienza.

Cholinesterase inhibitor (Altenuene) from an endophytic fungus Alternaria alternata: optimization, purification and characterization.

Science.gov (United States)

Bhagat, J; Kaur, A; Kaur, R; Yadav, A K; Sharma, V; Chadha, B S

2016-10-01

The aim of this study was to screen endophytic fungi isolated from Vinca rosea for their potential to produce acetylcholinesterase (AChE) inhibitors. Endophytic fungi isolated from V. rosea (Catharanthus roseus), were screened for AChE inhibitor production using Ellman's method. Maximum inhibition against AChE (78%) was observed in an isolate VS-10, identified to be Alternaria alternata on morphological and molecular basis. The isolate also inhibited butyrylcholinesterase (73%). Significant increase (1·3 fold) was achieved after optimization of process parameters using one variable at time approach. The inhibitor was purified using chromatographic techniques. The structure elucidation of the inhibitor was carried out using spectroscopic techniques and was identified to be 'altenuene'. The purified inhibitor possessed antioxidant potential as revealed by dot blot assay. The insecticidal potential of purified inhibitor was evaluated by feeding Spodoptora litura on diet amended with inhibitor. It evinced significant larval mortality. Endophytic A. alternata can serve as a source of dual cholinesterase inhibitor 'altenuene' with significant antioxidant and insecticidal activity. This is the first report on acetylcholinestearse inhibitory activity of altenuene. Alternaria alternata has the potential to produce a dual ChE inhibitor with antioxidant activity useful in the treatment of neurodegenerative disorders and in agriculture as biocontrol agent. © 2016 The Society for Applied Microbiology.

Effect of methyl parathion on the muscle and brain acetylcholinesterase activity of matrinxã (Brycon cephalus

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Almeida Luciana Cristina de

2005-01-01

Full Text Available Farming of the freshwater fish is emerging in Brazil and many species from the wild are promising. The teleost matrinxã (Brycon cephalus holds several characteristics such as fast growth rate, high commercial value and adaptability to artificial raring conditions, which make it a promising species for commerce. The use of pesticides in aquatic environment is frequent in Brazil, and methyl parathion is very common in aquaculture. We have determined the enzymatic activity of acetyl cholinesterase in white muscle and brain of matrinxã exposed to 2ppm of environmental methyl parathion for 24 hours. There was 64% and 69% of acetyl cholinesterase inhibition in muscle and brain respectively. These activities were not recovered after 8 days from exposure to this pesticide. It can be concluded that acetyl cholinesterase from those tissues was inhibited by small amounts of methyl parathion, and the main effect was observed in the brain.

Che: His Own Worst Enemy

Science.gov (United States)

2015-04-01

comprised of Green Berets, to go to Bolivia and train a Ranger battalion 40 in counter-insurgency operations. Leading this 16-man team was Maj...York: Routledge & Kegan Ltd., 1987. Sinclair, Andrew. Che Guevara. New York: The Viking Press, 1970. Study of the “Diary of ‘Che’ Guevara in

Assessment of serum level cholinesterase as a biomarker of liver cirrhosis in Egyptian cirrhotic patients

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Mona A. Amin

2017-09-01

Full Text Available Serum cholinesterase levels are closely correlated with the severity of liver disease. The aim of the paper was to assess the value of serum cholinesterase in evaluating liver reserve function in cirrhotic patients. 90 patients with liver cirrhosis and thirty healthy control group were included. Liver cirrhosis patients were classified according to child score into three equal groups: Child A liver cirrhosis, Child B liver cirrhosis and Child C liver cirrhosis. Patients were subjected to clinical evaluation, laboratory analysis, abdominal U/S. Measuring serum cholinesterase, and Calculation of both Child and model of end stage liver disease (MELD scores. The level of serum cholinesterase was higher in control group than the three groups of liver cirrhosis with median (IQR 17,410 (12,111-21,774, 7528 (5200-9856, 6021 (4500-7542, 3828.5 (1541-6060, respectively P<0.001. And the level of serum cholinesterase was higher in Child A more than Child B and Child C and the level of serum cholinesterase was higher in Child B more than Child C with very strong negative correlation between serum Cholinesterase level and Child score (r=-0.9, P<0.001. Also strong negative correlation between serum Cholinesterase level and MELD score (r=- 0.85, P=0.001, and positive correlation with prothrombin concentration (r=0.554, P=0.009, and serum albumin levels (r=0.582, P=0.0002. Serum cholinesterase is a good biomarker of cirrhosis. Since it distinguishes decompensated from compensated cirrhosis well, low levels in cirrhosis may serve as a useful prognostic marker of advanced liver disease.

Effects of cholinesterase inhibitors on the activities and protein levels of cholinesterases in the cerebrospinal fluid of patients with Alzheimer's disease: a review of recent clinical studies.

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Darreh-Shori, T; Soininen, H

2010-02-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline associated with a deficit in cholinergic function. Inhibitors of acetylcholinesterase (AChE) and/or butyrylcholinesterase (BuChE), such as donepezil, galantamine or rivastigmine, are widely prescribed as symptomatic treatments for AD. These agents exhibit a wide variation in their pharmacological properties. Here we review clinical data from 1998 to 2009 investigating the effect of different cholinesterase inhibitor treatments on the levels and activities of cholinesterases in the cerebrospinal fluid (CSF) of AD patients. These studies suggest that treatment with rapidly-reversible cholinesterase inhibitors (e.g. donepezil, galantamine, tacrine) are associated with marked and significant upregulation of AChE activities and protein levels in the CSF of AD patients. In contrast, pseudo-irreversible cholinesterase inhibition (e.g. rivastigmine) is associated with a significant decrease in both CSF AChE and BuChE activities, with no upregulation of CSF protein levels. Additionally, donepezil is associated with a decrease in the level of the AChE-R isoform relative to the synaptic AChE-S isoform, whereas rivastigmine seems to increase this ratio. These findings suggest that these agents exert different effects on CSF cholinesterases. The clinical effects of these pharmacological differences are yet to be fully established.

Optimization of Cholinesterase-Based Catalytic Bioscavengers Against Organophosphorus Agents.

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Lushchekina, Sofya V; Schopfer, Lawrence M; Grigorenko, Bella L; Nemukhin, Alexander V; Varfolomeev, Sergei D; Lockridge, Oksana; Masson, Patrick

2018-01-01

Organophosphorus agents (OPs) are irreversible inhibitors of acetylcholinesterase (AChE). OP poisoning causes major cholinergic syndrome. Current medical counter-measures mitigate the acute effects but have limited action against OP-induced brain damage. Bioscavengers are appealing alternative therapeutic approach because they neutralize OPs in bloodstream before they reach physiological targets. First generation bioscavengers are stoichiometric bioscavengers. However, stoichiometric neutralization requires administration of huge doses of enzyme. Second generation bioscavengers are catalytic bioscavengers capable of detoxifying OPs with a turnover. High bimolecular rate constants ( k cat / K m > 10 6 M -1 min -1 ) are required, so that low enzyme doses can be administered. Cholinesterases (ChE) are attractive candidates because OPs are hemi-substrates. Moderate OP hydrolase (OPase) activity has been observed for certain natural ChEs and for G117H-based human BChE mutants made by site-directed mutagenesis. However, before mutated ChEs can become operational catalytic bioscavengers their dephosphylation rate constant must be increased by several orders of magnitude. New strategies for converting ChEs into fast OPase are based either on combinational approaches or on computer redesign of enzyme. The keystone for rational conversion of ChEs into OPases is to understand the reaction mechanisms with OPs. In the present work we propose that efficient OP hydrolysis can be achieved by re-designing the configuration of enzyme active center residues and by creating specific routes for attack of water molecules and proton transfer. Four directions for nucleophilic attack of water on phosphorus atom were defined. Changes must lead to a novel enzyme, wherein OP hydrolysis wins over competing aging reactions. Kinetic, crystallographic, and computational data have been accumulated that describe mechanisms of reactions involving ChEs. From these studies, it appears that introducing

Optimization of Cholinesterase-Based Catalytic Bioscavengers Against Organophosphorus Agents

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Sofya V. Lushchekina

2018-03-01

Full Text Available Organophosphorus agents (OPs are irreversible inhibitors of acetylcholinesterase (AChE. OP poisoning causes major cholinergic syndrome. Current medical counter-measures mitigate the acute effects but have limited action against OP-induced brain damage. Bioscavengers are appealing alternative therapeutic approach because they neutralize OPs in bloodstream before they reach physiological targets. First generation bioscavengers are stoichiometric bioscavengers. However, stoichiometric neutralization requires administration of huge doses of enzyme. Second generation bioscavengers are catalytic bioscavengers capable of detoxifying OPs with a turnover. High bimolecular rate constants (kcat/Km > 106 M−1min−1 are required, so that low enzyme doses can be administered. Cholinesterases (ChE are attractive candidates because OPs are hemi-substrates. Moderate OP hydrolase (OPase activity has been observed for certain natural ChEs and for G117H-based human BChE mutants made by site-directed mutagenesis. However, before mutated ChEs can become operational catalytic bioscavengers their dephosphylation rate constant must be increased by several orders of magnitude. New strategies for converting ChEs into fast OPase are based either on combinational approaches or on computer redesign of enzyme. The keystone for rational conversion of ChEs into OPases is to understand the reaction mechanisms with OPs. In the present work we propose that efficient OP hydrolysis can be achieved by re-designing the configuration of enzyme active center residues and by creating specific routes for attack of water molecules and proton transfer. Four directions for nucleophilic attack of water on phosphorus atom were defined. Changes must lead to a novel enzyme, wherein OP hydrolysis wins over competing aging reactions. Kinetic, crystallographic, and computational data have been accumulated that describe mechanisms of reactions involving ChEs. From these studies, it appears that

Brain Training with Video Games in Covert Hepatic Encephalopathy.

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Bajaj, Jasmohan S; Ahluwalia, Vishwadeep; Thacker, Leroy R; Fagan, Andrew; Gavis, Edith A; Lennon, Michael; Heuman, Douglas M; Fuchs, Michael; Wade, James B

2017-02-01

Despite the associated adverse outcomes, pharmacologic intervention for covert hepatic encephalopathy (CHE) is not the standard of care. We hypothesized that a video game-based rehabilitation program would improve white matter integrity and brain connectivity in the visuospatial network on brain magnetic resonance imaging (MRI), resulting in improved cognitive function in CHE subjects on measures consistent with the cognitive skill set emphasized by the two video games (e.g., IQ Boost-visual working memory, and Aim and Fire Challenge-psychomotor speed), but also generalize to thinking skills beyond the focus of the cognitive training (Hopkins verbal learning test (HVLT)-verbal learning/memory) and improve their health-related quality of life (HRQOL). The trial included three phases over 8 weeks; during the learning phase (cognitive tests administered twice over 2 weeks without intervening intervention), training phase (daily video game training for 4 weeks), and post-training phase (testing 2 weeks after the video game training ended). Thirty CHE patients completed all visits with significant daily achievement on the video games. In a subset of 13 subjects that underwent brain MRI, there was a significant decrease in fractional anisotropy, and increased radial diffusivity (suggesting axonal sprouting or increased cross-fiber formation) involving similar brain regions (i.e., corpus callosum, internal capsule, and sections of the corticospinal tract) and improvement in the visuospatial resting-state connectivity corresponding to the video game training domains. No significant corresponding improvement in HRQOL or HVLT performance was noted, but cognitive performance did transiently improve on cognitive tests similar to the video games during training. Although multimodal brain imaging changes suggest reductions in tract edema and improved neural network connectivity, this trial of video game brain training did not improve the HRQOL or produce lasting improvement in

Selectivity of phenothiazine cholinesterase inhibitors for neurotransmitter systems.

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Darvesh, Sultan; Macdonald, Ian R; Martin, Earl

2013-07-01

Synthetic derivatives of phenothiazine have been used for over a century as well-tolerated drugs against a variety of human ailments from psychosis to cancer. This implies a considerable diversity in the mechanisms of action produced by structural changes to the phenothiazine scaffold. For example, chlorpromazine treatment of psychosis is related to its interaction with dopaminergic receptors. On the other hand, antagonistic action of such drugs on cholinergic receptor systems would be counter-productive for treatment of Alzheimer's disease. In a search for phenothiazines that are inhibitors of cholinesterases, especially butyrylcholinesterase, with potential to treat Alzheimer's disease, we wished to ascertain that such molecules could be devoid of neurotransmitter receptor interactions. To that end, a number of our synthetic N-10-carbonyl phenothiazine derivatives, with cholinesterase inhibitory activity, were tested for interaction with a variety of neurotransmitter receptor systems. We demonstrate that phenothiazines can be prepared without significant neurotransmitter receptor interactions while retaining high potency as cholinesterase ligands for treatment of Alzheimer's disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

à l'encoche sèche

African Journals Online (AJOL)

Chez Hevea brasiliensis, la production de latex est affectée par l'encoche sèche qui se manifeste par l'arrêt de l'écoulement de ... coagulation pour donner le caoutchouc naturel. ..... relationship between latex sugar content, the metabolic ...

21 CFR 862.3240 - Cholinesterase test system.

Science.gov (United States)

2010-04-01

... obtained by this device are used in the diagnosis and treatment of cholinesterase inhibition disorders (e.g., insecticide poisoning and succinylcholine poisoning). (b) Classification. Class I. ...

New Indole Alkaloids from the Bark of Rauvolfia Reflexa and their Cholinesterase Inhibitory Activity

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Mehran Fadaeinasab

2015-11-01

Full Text Available Background/Aims: Rauvolfia reflexa is a member of the Apocynaceae family. Plants from the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders Methods and Results: Two new indole alkaloids, rauvolfine C (1 and 3-methyl-10,11-dimethoxy-6-methoxycarbonyl-β-carboline (2, along with five known, macusine B (3, vinorine (4, undulifoline (5, isoresrpiline (6 and rescinnamine (7 were isolated from the bark of Rauvolfia reflexa. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The compounds showed good to moderate cholinesterase inhibitory activity with IC50 values in the range of 8.06 to 73.23 µM. Compound 7 was found to be the most potent inhibitor of both acetylcholinesterase (AChE and butyrylcholinesterase (BChE. Compounds 1, 2, 5 and 6 were found to be selective towards BChE, while compounds 3, 4 and 7 were dual inhibitors, having almost equal inhibitory activity on both AChE and BChE. Molecular docking revealed that compounds 6 and 7 interacted differently on AChE and BChE, by means of hydrophobic interactions and hydrogen bonding. In AChE, the indole moiety of both compounds interacted with the residues lining the peripheral anionic site, whereas in BChE, their methoxy groups are primarily responsible for the strong inhibitory activity via interactions with residues at the active site of the enzyme. Conclusion: Two new and five known indole alkaloids were isolated from R. reflexa. Among the compounds, 7 and 6 showed the most potent and promising cholinesterase inhibitory activity, worthy for further investigations.

New Indole Alkaloids from the Bark of Rauvolfia Reflexa and their Cholinesterase Inhibitory Activity.

Science.gov (United States)

Fadaeinasab, Mehran; Basiri, Alireza; Kia, Yalda; Karimian, Hamed; Ali, Hapipah Mohd; Murugaiyah, Vikneswaran

2015-01-01

Rauvolfia reflexa is a member of the Apocynaceae family. Plants from the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders Methods and Results: Two new indole alkaloids, rauvolfine C (1) and 3-methyl-10,11-dimethoxy-6-methoxycarbonyl-β-carboline (2), along with five known, macusine B (3), vinorine (4), undulifoline (5), isoresrpiline (6) and rescinnamine (7) were isolated from the bark of Rauvolfia reflexa. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The compounds showed good to moderate cholinesterase inhibitory activity with IC50 values in the range of 8.06 to 73.23 µM. Compound 7 was found to be the most potent inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1, 2, 5 and 6 were found to be selective towards BChE, while compounds 3, 4 and 7 were dual inhibitors, having almost equal inhibitory activity on both AChE and BChE. Molecular docking revealed that compounds 6 and 7 interacted differently on AChE and BChE, by means of hydrophobic interactions and hydrogen bonding. In AChE, the indole moiety of both compounds interacted with the residues lining the peripheral anionic site, whereas in BChE, their methoxy groups are primarily responsible for the strong inhibitory activity via interactions with residues at the active site of the enzyme. Two new and five known indole alkaloids were isolated from R. reflexa. Among the compounds, 7 and 6 showed the most potent and promising cholinesterase inhibitory activity, worthy for further investigations. © 2015 S. Karger AG, Basel.

The Azospirillum brasilense Che1 chemotaxis pathway controls swimming velocity, which affects transient cell-to-cell clumping.

Science.gov (United States)

Bible, Amber; Russell, Matthew H; Alexandre, Gladys

2012-07-01

The Che1 chemotaxis-like pathway of Azospirillum brasilense contributes to chemotaxis and aerotaxis, and it has also been found to contribute to regulating changes in cell surface adhesive properties that affect the propensity of cells to clump and to flocculate. The exact contribution of Che1 to the control of chemotaxis and flocculation in A. brasilense remains poorly understood. Here, we show that Che1 affects reversible cell-to-cell clumping, a cellular behavior in which motile cells transiently interact by adhering to one another at their nonflagellated poles before swimming apart. Clumping precedes and is required for flocculation, and both processes appear to be independently regulated. The phenotypes of a ΔaerC receptor mutant and of mutant strains lacking cheA1, cheY1, cheB1, or cheR1 (alone or in combination) or with che1 deleted show that Che1 directly mediates changes in the flagellar swimming velocity and that this behavior directly modulates the transient nature of clumping. Our results also suggest that an additional receptor(s) and signaling pathway(s) are implicated in mediating other Che1-independent changes in clumping identified in the present study. Transient clumping precedes the transition to stable clump formation, which involves the production of specific extracellular polysaccharides (EPS); however, production of these clumping-specific EPS is not directly controlled by Che1 activity. Che1-dependent clumping may antagonize motility and prevent chemotaxis, thereby maintaining cells in a metabolically favorable niche.

Structure-Based Search for New Inhibitors of Cholinesterases

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Barbara Malawska

2013-03-01

Full Text Available Cholinesterases are important biological targets responsible for regulation of cholinergic transmission, and their inhibitors are used for the treatment of Alzheimer’s disease. To design new cholinesterase inhibitors, of different structure-based design strategies was followed, including the modification of compounds from a previously developed library and a fragment-based design approach. This led to the selection of heterodimeric structures as potential inhibitors. Synthesis and biological evaluation of selected candidates confirmed that the designed compounds were acetylcholinesterase inhibitors with IC50 values in the mid-nanomolar to low micromolar range, and some of them were also butyrylcholinesterase inhibitors.

Che a 1: recombinant expression, purification and correspondence to the natural form.

Science.gov (United States)

Barderas, Rodrigo; Villalba, Mayte; Rodríguez, Rosalía

2004-12-01

Pollinosis to chenopods is one of the main causes of allergy in desertic regions and it is increasing in the South of Europe and Western USA. Che a 1 is a major allergen for chenopod-allergic subjects and belongs to the Ole-e-1-like family of proteins. Pichia pastoris yeast has been used as expression system to produce the recombinant form of Che a 1 (rChe a 1). The allergen was isolated using a gel permeation column and reverse-phase/high-performance liquid chromatography. Molecular characterization was performed using Edman degradation, mass spectrometry and concanavalin A staining. Sera from patients allergic to chenopod pollen, as well as polyclonal and monoclonal antibodies raised against Ole e 1, were used in immunoblotting, ELISA and inhibition assays for immunological characterization of rChe a 1. The allergen was purified to homogeneity with a final yield of 15 mg/l of cell culture and showed a glycosylated character. N-terminal amino acid sequence of rChe a 1 and molecular mass were according to those of the protein isolated from chenopod pollen. The recombinant allergen maintained the IgG and IgE epitopes of the natural allergen deduced from the immunological assays. Structural and in vitro immunological properties of rChe a 1 produced in P. pastoris were equivalent to those of the natural form of the allergen and, thus, it could be used in testing patients allergic to chenopods. 2004 S. Karger AG, Basel.

Development of a Physiologically Based Pharmacokinetic and Pharmacodynamic Model to Determine Dosimetry and Cholinesterase Inhibition for a Binary Mixture of Chlorpyrifos and Diazinon in the Rat

Energy Technology Data Exchange (ETDEWEB)

Timchalk, Chuck; Poet, Torka S.

2008-05-01

Physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models have been developed and validated for the organophosphorus (OP) insecticides chlorpyrifos (CPF) and diazinon (DZN). Based on similar pharmacokinetic and mode of action properties it is anticipated that these OPs could interact at a number of important metabolic steps including: CYP450 mediated activation/detoxification, and blood/tissue cholinesterase (ChE) binding/inhibition. We developed a binary PBPK/PD model for CPF, DZN and their metabolites based on previously published models for the individual insecticides. The metabolic interactions (CYP450) between CPF and DZN were evaluated in vitro and suggests that CPF is more substantially metabolized to its oxon metabolite than is DZN. These data are consistent with their observed in vivo relative potency (CPF>DZN). Each insecticide inhibited the other’s in vitro metabolism in a concentration-dependent manner. The PBPK model code used to described the metabolism of CPF and DZN was modified to reflect the type of inhibition kinetics (i.e. competitive vs. non-competitive). The binary model was then evaluated against previously published rodent dosimetry and ChE inhibition data for the mixture. The PBPK/PD model simulations of the acute oral exposure to single- (15 mg/kg) vs. binary-mixtures (15+15 mg/kg) of CFP and DZN at this lower dose resulted in no differences in the predicted pharmacokinetics of either the parent OPs or their respective metabolites; whereas, a binary oral dose of CPF+DZN at 60+60 mg/kg did result in observable changes in the DZN pharmacokinetics. Cmax was more reasonably fit by modifying the absorption parameters. It is anticipated that at low environmentally relevant binary doses, most likely to be encountered in occupational or environmental related exposures, that the pharmacokinetics are expected to be linear, and ChE inhibition dose-additive.

PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos

International Nuclear Information System (INIS)

Ellison, Corie A.; Crane, Alice L.; Bonner, Matthew R.; Knaak, James B.; Browne, Richard W.; Lein, Pamela J.; Olson, James R.

2012-01-01

Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and urine were collected from agricultural workers (n = 120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P ≤ 0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P ≤ 0.05) and PON1 192 (P ≤ 0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal. -- Highlights: ► CPF exposure resulted in an increase in TCPy and decreases in BuChE and AChE. ► CPOase activity decreased in subjects with the PON1 55LM and PON1 55 MM genotypes. ► Neither PON1 genotype nor CPOase activity had an effect on BuChE or AChE inhibition.

PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos

Energy Technology Data Exchange (ETDEWEB)

Ellison, Corie A., E-mail: cellison@buffalo.edu [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Crane, Alice L., E-mail: alcrane@buffalo.edu [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Bonner, Matthew R., E-mail: mrbonner@buffalo.edu [Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Knaak, James B., E-mail: jbknaak@aol.com [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Browne, Richard W., E-mail: rwbrowne@buffalo.edu [Department of Biotechnical and Clinical Laboratory Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Lein, Pamela J., E-mail: pjlein@ucdavis.edu [Department of Molecular Biosciences, University of California School of Veterinary Medicine, Davis, CA 95618 (United States); Olson, James R., E-mail: jolson@buffalo.edu [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY 14214 (United States)

2012-12-15

Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and urine were collected from agricultural workers (n = 120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P ≤ 0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P ≤ 0.05) and PON1 192 (P ≤ 0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal. -- Highlights: ► CPF exposure resulted in an increase in TCPy and decreases in BuChE and AChE. ► CPOase activity decreased in subjects with the PON1 55LM and PON1 55 MM genotypes. ► Neither PON1 genotype nor CPOase activity had an effect on BuChE or AChE inhibition.

A direct method to visualise the aryl acylamidase activity on cholinesterases in polyacrylamide gels

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Boopathy Rathanam

2000-12-01

Full Text Available Abstract Background In vertebrates, two types of cholinesterases exist, acetylcholinesterase and butyrylcholinesterase. The function of acetylcholinesterase is to hydrolyse acetylcholine, thereby terminating the neurotransmission at cholinergic synapse, while the precise physiological function of butyrylcholinesterase has not been identified. The presence of cholinesterases in tissues that are not cholinergically innervated indicate that cholinesterases may have functions unrelated to neurotransmission. Furthermore, cholinesterases display a genuine aryl acylamidase activity apart from their predominant acylcholine hydrolase activity. The physiological significance of this aryl acylamidase activity is also not known. The study on the aryl acylamidase has been, in part hampered by the lack of a specific method to visualise this activity. We have developed a method to visualise the aryl acylamidase activity on cholinesterase in polyacrylamide gels. Results The o-nitroaniline liberated from o-nitroacetanilide by the action of aryl acylamidase activity on cholinesterases, in the presence of nitrous acid formed a diazonium compound. This compound gave an azo dye complex with N-(1-napthyl-ethylenediamine, which appeared as purple bands in polyacrylamide gels. Treating the stained gels with trichloroacetic acid followed by Tris-HCl buffer helped in fixation of the stain in the gels. By using specific inhibitors for acetylcholinesterase and butyrylcholinesterase, respectively, differential staining for the aryl acylamidase activities on butyrylcholinesterase and acetylcholinesterase in a sample containing both these enzymes has been demonstrated. A linear relationship between the intensity of colour developed and activity of the enzyme was obtained. Conclusions A novel method to visualise the aryl acylamidase activity on cholinesterases in polyacrylamide gels has been developed.

[Levels of plasma cholinesterase in Colombian working-class populations].

Science.gov (United States)

Carmona-Fonseca, Jaime

2003-12-01

Levels of plasma cholinesterase in Colombian working-class populations Reference values for plasma cholinesterase (EC 3.1.1.8) are not available for Colombian populations. A representative sample of a working-class population was used to establish these values to provide reference data for use by the social security system. Two working-class populations were sampled from the Aburrá Valley (Aburrá) and eastern Antioquia (Oriente). Cholinesterase activity was measured in 827 workers, with ages spanning 18-49 years, 415 from Aburrá and 412 people from Oriente. Three methods were used to measure cholinesterase: Michel, EQM and Monotest The average values by Michel and EQM were not statistically different between regions (Michel: Aburrá, 1.11, and East, 1.13 deltas pH/hora; EQM: Aburrá, 2.55, and Oriente, 2.48 U/ml). By the Monotest, the enzyme average was statistically higher in Aburra than in Oriente (5,743 and 5,459 U/L respectively; p = 0 .012). By region and technique, men had significantly higher enzymatic levels than women. Within both regions and sexes, no statistically significant difference among the three aged groups was noted. Our obtained Colombian values differed significantly from foreign reference values: Michel and Monotest levels were higher and EQM levels were lower. For making clinical and epidemiologic decisions in Colombia related to these data, the values obtained for the Colombian populations are preferred over values derived from external sources.

Lycopene modulates cholinergic dysfunction, Bcl-2/Bax balance, and antioxidant enzymes gene transcripts in monosodium glutamate (E621) induced neurotoxicity in a rat model.

Science.gov (United States)

Sadek, Kadry; Abouzed, Tarek; Nasr, Sherif

2016-04-01

The effect of monosodium glutamate (MSG) on brain tissue and the relative ability of lycopene to avert these neurotoxic effects were investigated. Thirty-two male Wistar rats were distributed into 4 groups: group I, untreated (placebo); group II, injected with MSG (5 mg·kg(-1)) s.c.; group III, gastrogavaged with lycopene (10 mg·kg(-1)) p.o.; and group IV received MSG with lycopene with the same mentioned doses for 30 days. The results showed that MSG induced elevation in lipid peroxidation marker and perturbation in the antioxidant homeostasis and increased the levels of brain and serum cholinesterase (ChE), total creatine phosphokinase (CPK), creatine phosphokinase isoenzymes BB (CPK-BB), and lactate dehydrogenase (LDH). Glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities and gene expression were increased and glutathione content was reduced in the MSG-challenged rats, and these effects were ameliorated by lycopene. Furthermore, MSG induced apoptosis in brain tissues reflected in upregulation of pro-apoptotic Bax while lycopene upregulated the anti-apoptotic Bcl-2. Our results indicate that lycopene appears to be highly effective in relieving the toxic effects of MSG by inhibiting lipid peroxidation and inducing modifications in the activity of cholinesterase and antioxidant pathways. Interestingly, lycopene protects brain tissue by inhibiting apoptosis signaling induced by MSG.

Overexpression, purification, crystallization and preliminary X-ray analysis of CheY4 from Vibrio cholerae O395

International Nuclear Information System (INIS)

Biswas, Maitree; Khamrui, Susmita; Sen, Udayaditya; Dasgupta, Jhimli

2011-01-01

The chemotaxis response regulator CheY4 from V. cholerae has been cloned, overexpressed, purified and crystallized in monoclinic and hexagonal space groups; the crystals diffracted to 1.67 and 1.9 Å resolution, respectively. Chemotaxis and motility greatly influence the infectivity of Vibrio cholerae, although the role of chemotaxis genes in V. cholerae pathogenesis is poorly understood. In contrast to the single copy of CheY found in Escherichia coli and Salmonella typhimurium, four CheYs (CheY1–CheY4) are present in V. cholerae. While insertional disruption of the cheY4 gene results in decreased motility, insertional duplication of this gene increases motility and causes enhanced expression of the two major virulence genes. Additionally, cheY3/cheY4 influences the activation of the transcription factor NF-κB, which triggers the generation of acute inflammatory responses. V. cholerae CheY4 was cloned, overexpressed and purified by Ni–NTA affinity chromatography followed by gel filtration. Crystals of CheY4 grown in space group C2 diffracted to 1.67 Å resolution, with unit-cell parameters a = 94.4, b = 31.9, c = 32.6 Å, β = 96.5°, whereas crystals grown in space group P3 2 21 diffracted to 1.9 Å resolution, with unit-cell parameters a = b = 56.104, c = 72.283 Å, γ = 120°

Crystal Structure of the Extracellular Cholinesterase-Like Domain from Neuroligin-2

Energy Technology Data Exchange (ETDEWEB)

Koehnke,J.; Jin, X.; Budreck, E.; Posy, S.; Scheiffele, P.; Hnoig, B.; Shapiro, L.

2008-01-01

Neuroligins (NLs) are catalytically inactive members of a family of cholinesterase-like transmembrane proteins that mediate cell adhesion at neuronal synapses. Postsynaptic neuroligins engage in Ca2+-dependent transsynaptic interactions via their extracellular cholinesterase domain with presynaptic neurexins (NRXs). These interactions may be regulated by two short splice insertions (termed A and B) in the NL cholinesterase domain. Here, we present the 3.3- Angstroms crystal structure of the ectodomain from NL2 containing splice insertion A (NL2A). The overall structure of NL2A resembles that of cholinesterases, but several structural features are unique to the NL proteins. First, structural elements surrounding the esterase active-site region differ significantly between active esterases and NL2A. On the opposite surface of the NL2A molecule, the positions of the A and B splice insertions identify a candidate NRX interaction site of the NL protein. Finally, sequence comparisons of NL isoforms allow for mapping the location of residues of previously identified mutations in NL3 and NL4 found in patients with autism spectrum disorders. Overall, the NL2 structure promises to provide a valuable model for dissecting NL isoform- and synapse-specific functions.

Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials

OpenAIRE

Kaduszkiewicz, Hanna; Zimmermann, Thomas; Beck-Bornholdt, Hans-Peter; van den Bussche, Hendrik

2005-01-01

Objectives Pharmacological treatment of Alzheimer's disease focuses on correcting the cholinergic deficiency in the central nervous system with cholinesterase inhibitors. Three cholinesterase inhibitors are currently recommended: donepezil, rivastigmine, and galantamine. This review assessed the scientific evidence for the recommendation of these agents.

Oestrogen, testosterone, cytotoxin and cholinesterase inhibitor ...

African Journals Online (AJOL)

Oestrogen, testosterone, cytotoxin and cholinesterase inhibitor removal during reclamation of sewage to drinking water. ... Risks associated with sewage effluent and reclaimed sewage should be closely monitored; therefore water at the Gammams Sewage Treatment Plant (GSTP) inlet and outlet, as well as reclaimed water ...

His Excellency Professor Dr Che-Ho Wei, Chairman, National Science Council Executive Yuan, Republic of China

CERN Multimedia

Patrice Loïez

2002-01-01

Photo 01: Professor Dr. Che-Ho Wei signing the Guest Book with CERN Director-General, L. Maiani. Photo 02: Professor Dr. Che-Ho Wei. Photo 03::Professor Dr. Che-Ho Wei shaking hands with CERN Director-General, L. Maiani.

Pro-2-PAM therapy for central and peripheral cholinesterases.

Science.gov (United States)

Demar, James C; Clarkson, Edward D; Ratcliffe, Ruthie H; Campbell, Amy J; Thangavelu, Sonia G; Herdman, Christine A; Leader, Haim; Schulz, Susan M; Marek, Elizabeth; Medynets, Marie A; Ku, Therese C; Evans, Sarah A; Khan, Farhat A; Owens, Roberta R; Nambiar, Madhusoodana P; Gordon, Richard K

2010-09-06

Novel therapeutics to overcome the toxic effects of organophosphorus (OP) chemical agents are needed due to the documented use of OPs in warfare (e.g. 1980-1988 Iran/Iraq war) and terrorism (e.g. 1995 Tokyo subway attacks). Standard OP exposure therapy in the United States consists of atropine sulfate (to block muscarinic receptors), the acetylcholinesterase (AChE) reactivator (oxime) pralidoxime chloride (2-PAM), and a benzodiazepine anticonvulsant to ameliorate seizures. A major disadvantage is that quaternary nitrogen charged oximes, including 2-PAM, do not cross the blood brain barrier (BBB) to treat brain AChE. Therefore, we have synthesized and evaluated pro-2-PAM (a lipid permeable 2-PAM derivative) that can enter the brain and reactivate CNS AChE, preventing seizures in guinea pigs after exposure to OPs. The protective effects of the pro-2-PAM after OP exposure were shown using (a) surgically implanted radiotelemetry probes for electroencephalogram (EEG), (b) neurohistopathology of brain, (c) cholinesterase activities in the PNS and CNS, and (d) survivability. The PNS oxime 2-PAM was ineffective at reducing seizures/status epilepticus (SE) in diisopropylfluorophosphate (DFP)-exposed animals. In contrast, pro-2-PAM significantly suppressed and then eliminated seizure activity. In OP-exposed guinea pigs, there was a significant reduction in neurological damage with pro-2-PAM but not 2-PAM. Distinct regional areas of the brains showed significantly higher AChE activity 1.5h after OP exposure in pro-2-PAM treated animals compared to the 2-PAM treated ones. However, blood and diaphragm showed similar AChE activities in animals treated with either oxime, as both 2-PAM and pro-2-PAM are PNS active oximes. In conclusion, pro-2-PAM can cross the BBB, is rapidly metabolized inside the brain to 2-PAM, and protects against OP-induced SE through restoration of brain AChE activity. Pro-2-PAM represents the first non-invasive means of administering a CNS therapeutic for

Il fantasma dell'universo che cos'è il neutrino

CERN Document Server

Votano, Lucia

2015-01-01

Ben prima della luce, a un decimillesimo di secondo dal Big Bang, i neutrini sono apparsi nell'universo. Dopo un secondo il brodo primordiale si era raffreddato abbastanza da consentire loro di muoversi liberi e ancora oggi, dopo quasi quattordici miliardi di anni, sono numerosissimi. Ma che cosa sono i neutrini? Elusivi come fantasmi, camaleontici, viaggiano indenni attraverso la materia arrivando dritti sino a noi dagli angoli più remoti e nascosti dell'universo. Per saperne di più seguiremo i fisici che li studiano in laboratori sotterranei o in luoghi estremi come i ghiacciai polari o le profondità marine.

Coumarins as cholinesterase inhibitors: A review.

Science.gov (United States)

de Souza, Luana G; Rennã, Magdalena N; Figueroa-Villar, Jose D

2016-07-25

The first report in literature of the isolation of coumarin was in the year 1820. After this report, other papers were published demonstrating the isolation and synthesis of coumarin and analogues. These compounds have been studying along the years for several different pathologies. One of these pathologies was Alzheimer's disease (AD), being the main cause of dementia in the contemporary world. There are two hypotheses to explain the pathogenesis mechanism and disease symptoms, then having the "amyloid hypothesis" and the "cholinergic hypothesis". Some drugs for AD are based on the theory of "cholinergic hypothesis", which objective is to increase the concentration of ACh in the synaptic cleft by the inhibition of cholinesterases. Over the last twenty years, many studies with coumarins compounds were reported as cholinesterases inhibitors. The aim of the present review is to discuss the studies and development of new compounds for AD treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Serum cholinesterase activity in infantile and juvenile spinal muscular atrophy.

Science.gov (United States)

Niebroj-Dobosz, I; Hausmanowa-Petrusewicz, I

1989-09-01

Serum acetylcholinesterase (AChE) and pseudocholinesterase (ChE) activity in infantile and juvenile spinal muscular atrophy (SMA) was determined. The total AChE activity was either normal or decreased in the childhood SMA (Type 1), the other SMA groups and disease controls (ALS, X-linked SMA). In the majority of SMA Type 1 cases (6/7 tested) an absence of the asymmetric A12 form was found. This was accompanied by changes in the other asymmetric and globular forms. The latter was, however, not specific for SMA Type 1 cases. The ChE activity was increased in the majority of SMA cases as well as disease controls. The asymmetric A12 ChE form was increased in all SMA Type 3 cases, the values of this form in SMA Type 1 was variable. A change in the ChE globular forms in SMA Type 1 and SMA Type 2 was a frequent finding. It is suggested that the absence of the asymmetric A12 AChE form in SMA Type 1 arises because of muscle cell immaturity and undeveloped muscle-nerve interactions. The reason of ChE changes is obscure.

The Emotional Communication in Hearing Questionnaire (EMO-CHeQ): Development and Evaluation.

Science.gov (United States)

Singh, Gurjit; Liskovoi, Lisa; Launer, Stefan; Russo, Frank

2018-06-11

The objectives of this research were to develop and evaluate a self-report questionnaire (the Emotional Communication in Hearing Questionnaire or EMO-CHeQ) designed to assess experiences of hearing and handicap when listening to signals that contain vocal emotion information. Study 1 involved internet-based administration of a 42-item version of the EMO-CHeQ to 586 adult participants (243 with self-reported normal hearing [NH], 193 with self-reported hearing impairment but no reported use of hearing aids [HI], and 150 with self-reported hearing impairment and use of hearing aids [HA]). To better understand the factor structure of the EMO-CHeQ and eliminate redundant items, an exploratory factor analysis was conducted. Study 2 involved laboratory-based administration of a 16-item version of the EMO-CHeQ to 32 adult participants (12 normal hearing/near normal hearing (NH/nNH), 10 HI, and 10 HA). In addition, participants completed an emotion-identification task under audio and audiovisual conditions. In study 1, the exploratory factor analysis yielded an interpretable solution with four factors emerging that explained a total of 66.3% of the variance in performance the EMO-CHeQ. Item deletion resulted in construction of the 16-item EMO-CHeQ. In study 1, both the HI and HA group reported greater vocal emotion communication handicap on the EMO-CHeQ than on the NH group, but differences in handicap were not observed between the HI and HA group. In study 2, the same pattern of reported handicap was observed in individuals with audiometrically verified hearing as was found in study 1. On the emotion-identification task, no group differences in performance were observed in the audiovisual condition, but group differences were observed in the audio alone condition. Although the HI and HA group exhibited similar emotion-identification performance, both groups performed worse than the NH/nNH group, thus suggesting the presence of behavioral deficits that parallel self

Assessment of Subchronic Neurobehaviorial and Neuropathologic Effects in Rats Following Low-Level Sarin Exposure

National Research Council Canada - National Science Library

Olson, Carl

1999-01-01

.... Doses of pyridostigmine bromide (PB) i.m., Sarin (GB) s.c., and chlorpyrifos (CPF) topically which produced approximately 20-30, 5-10, and 5-10 percent whole blood cholinesterase inhibition (ChE...

The new Meyrin crèche takes its first steps

CERN Multimedia

2008-01-01

The new Meyrin crèche was inaugurated on 10 October and already caters for 16 children of CERN personnel. Copyright: Laurent Barlier. Copyright: Robert Tillmann. At the end of August, the new Meyrin crèche in Champs-Fréchets, the Espace de Vie Enfantine (EVE), welcomed its first intake of infants. They included 16 children of members of the CERN personnel who are benefiting from the agreement signed in 2007 with the commune of Meyrin (see Bulletin n°43&44/2007). The crèche was officially inaugurated on 10 October with several CERN representatives in attendance, including HR Department Head, Enrico Chiaveri, and Head of the Relations with the Host States Service, Friedmann Eder. The following day, EVE held an open day for the inhabitants of Meyrin and interested members of the CERN personnel. The new 1516 m2 building ‘s spaces have very clean and ...

Evaluation of Cholinesterase Activities During in Vivo Intoxication Using an Electrochemical Sensor Strip – Correlation With Intoxication Symptoms

Directory of Open Access Journals (Sweden)

Jana Zdarova-Karasova

2009-05-01

Full Text Available Cholinesterase activity in blood of laboratory rats was monitored. Rats were intoxicated with paraoxon at dosis of 0 – 65 – 125 – 170 – 250 – 500 nmol. The 250 nmol dose was found to be the LD50. An electrochemical sensor was found useful to provide information about cholinesterase activity. The decrease of cholinesterase activity was correlated to intoxication symptoms and mortality level. It was found that the symptoms of intoxication are not observed while at least 50% of cholinesterase activity in blood remains. The minimal cholinesterase activity essential to survival is around 10%, when compared with the initial state. No changes in levels of low moleculary weight antioxidants were observed.

Phosphorylated Derivatives of Alkaloids and Nitrogen-containing Heterocycles — Cholinesterase Inhibitors

Science.gov (United States)

Sadykov, Abid S.; Dalimov, D. N.; Godovikov, Nikolai N.

1983-10-01

The review deals with the synthesis and anticholinesterase activities of phosphorylated derivatives of certain alkaloids and nitrogen-containing heterocycles. It is shown that the conformational properties of the alkaloid and nitrogen-containing heterocycle residues in the composition of the organophosphorus inhibitor (OPI) molecule play an important role in the inhibition of the catalytic activity of cholinesterases. The type of inhibition of cholinesterases also varies as a function of chemical structure. The bibliography includes 45 references.

Pharmacokinetic and pharmacodynamic interaction for a binary mixture of chlorpyrifos and diazinon in the rat

International Nuclear Information System (INIS)

Timchalk, C.; Poet, T.S.; Hinman, M.N.; Busby, A.L.; Kousba, A.A.

2005-01-01

Chlorpyrifos (CPF) and diazinon (DZN) are two commonly used organophosphorus (OP) insecticides and a potential exists for concurrent exposures. The primary neurotoxic effects from OP pesticide exposures result from the inhibition of acetylcholinesterase (AChE). The pharmacokinetic and pharmacodynamic impact of acute binary exposures of rats to CPF and DZN was evaluated in this study. Rats were orally administered CPF, DZN, or a CPF/DZN mixture (0, 15, 30, or 60 mg/kg) and blood (plasma and RBC), and brain were collected at 0, 3, 6, 12, and 24 h postdosing, urine was also collected at 24 h. Chlorpyrifos, DZN, and their respective metabolites, 3,5,6-trichloro-2-pyridinol (TCP) and 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMHP), were quantified in blood and/or urine and cholinesterase (ChE) inhibition was measured in brain, RBC, and plasma. Coexposure to CPF/DZN at the low dose of 15/15 mg/kg did not alter the pharmacokinetics of CPF, DZN, or their metabolites in blood. A high binary dose of 60/60 mg/kg increased the C max and AUC and decreased the clearance for both parent compounds, likely due to competition between CPF and DZN for CYP450 metabolism. At lower doses, most likely to be encountered in occupational or environmental exposures, the pharmacokinetics were linear. A dose-dependent inhibition of ChE was noted in tissues for both the single and coexposures, and the extent of inhibition was plasma > RBC ≥ brain. The overall relative potency for ChE inhibition was CPF/DZN > CPF > DZN. A comparison of the ChE response at the low binary dose (15/15 mg/kg), where there were no apparent pharmacokinetic interactions, suggested that the overall ChE response was additive. These experiments represent important data concerning the potential pharmacokinetic and pharmacodynamic interactions for pesticide mixtures and will provide needed insight for assessing the potential cumulative risk associated with occupational or environmental exposures to these insecticides

MSL Chemistry and Mineralogy X-Ray Diffraction X-Ray Fluorescence (CheMin) Instrument

Science.gov (United States)

Zimmerman, Wayne; Blake, Dave; Harris, William; Morookian, John Michael; Randall, Dave; Reder, Leonard J.; Sarrazin, Phillipe

2013-01-01

This paper provides an overview of the Mars Science Laboratory (MSL) Chemistry and Mineralogy Xray Diffraction (XRD), X-ray Fluorescence (XRF) (CheMin) Instrument, an element of the landed Curiosity rover payload, which landed on Mars in August of 2012. The scientific goal of the MSL mission is to explore and quantitatively assess regions in Gale Crater as a potential habitat for life - past or present. The CheMin instrument will receive Martian rock and soil samples from the MSL Sample Acquisition/Sample Processing and Handling (SA/SPaH) system, and process it utilizing X-Ray spectroscopy methods to determine mineral composition. The Chemin instrument will analyze Martian soil and rocks to enable scientists to investigate geophysical processes occurring on Mars. The CheMin science objectives and proposed surface operations are described along with the CheMin hardware with an emphasis on the system engineering challenges associated with developing such a complex instrument.

Finally, a crèche at CERN!

CERN Multimedia

Anaïs Schaeffer

2013-01-01

After many years of discussion, the CERN Staff Association’s first crèche will open its doors in September to welcome up to 20 babies and toddlers.   A delicate operation: the installation of 11 modules above the Nursery's School canteen. Image: Sigrid Knoops. The CERN Staff Association’s Nursery School, which will soon turn 50, is pleased to announce the establishment of CERN’s first crèche. This project, which has come to fruition over the past academic year with the support of the CERN Management, meets an established and growing need among the Laboratory’s personnel and users. As a modular construction, the Nursery School’s new second floor was assembled above the existing canteen in a matter of days. Its 11 modules are ultra-modern – they’re even equipped with underfloor heating. “Thanks to this extension, we will be able to accept around twenty babies at the start of the academ...

Plasma B-esterase activities in European raptors.

Science.gov (United States)

Roy, Claudie; Grolleau, Gérard; Chamoulaud, Serge; Rivière, Jean-Louis

2005-01-01

B-esterases are serine hydrolases composed of cholinesterases, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and carboxylesterase (CbE). These esterases, found in blood plasma, are inhibited by organophosphorus (OP) and carbamate (CB) insecticides and can be used as nondestructive biomarkers of exposure to anticholinesterase insecticides. Furthermore, B-esterases are involved in detoxification of these insecticides. In order to establish the level of these enzymes and to have reference values for their normal activities, total plasma cholinesterase (ChE), AChE and BChE activities, and plasma CbE activity were determined in 729 European raptors representing 20 species, four families, and two orders. The diurnal families of the Falconiforme order were represented by Accipitridae and Falconidae and the nocturnal families of the Strigiforme order by Tytonidae and Strigidae. Intraspecies differences in cholinesterase activities according to sex and/or age were investigated in buzzards (Buteo buteo), sparrowhawks (Accipiter nisus), kestrels (Falco tinnunculus), barn owls (Tyto alba), and tawny owls (Strix aluco). Sex-related differences affecting ChE and AChE activities were observed in young kestrels (2-3-mo-old) and age-related differences in kestrels (ChE and AChE), sparrowhawks (AChE), and tawny owls (ChE, AChE, and BChE). The interspecies analysis yielded a negative correlation between ChE activity and body mass taking into account the relative contribution of AChE and BChE to ChE activity, with the exception of the honey buzzard (Pernis apivorus). The lowest ChE activities were found in the two largest species, Bonelli's eagle (Hieraaetus fasciatus) and Egyptian vulture (Neophron percnopterus) belonging to the Accipitridae family. The highest ChE activities were found in the relatively small species belonging to the Tytonidae and Strigidae families and in honey buzzard of the Accipitridae family. Species of the Accipitridae, Tytonidae, and

Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

Directory of Open Access Journals (Sweden)

Magdalena Markowicz-Piasecka

2017-01-01

Full Text Available The results of epidemiological and pathophysiological studies suggest that type 2 diabetes mellitus (T2DM may predispose to Alzheimer’s disease (AD. The two conditions present similar glucose levels, insulin resistance, and biochemical etiologies such as inflammation and oxidative stress. The diabetic state also contributes to increased acetylcholinesterase (AChE activity, which is one of the factors leading to neurodegeneration in AD. The aim of this study was to assess in vitro the effects of metformin, phenformin, and metformin sulfenamide prodrugs on the activity of human AChE and butyrylcholinesterase (BuChE and establish the type of inhibition. Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 μmol/mL, mixed type of inhibition and seemed to be selective towards AChE since it presented low anti-BuChE activity. The tested metformin prodrugs inhibited cholinesterases (ChE at nanomolar range and thus were more active than metformin or phenformin. The cyclohexyl sulfenamide prodrug demonstrated the highest activity towards both AChE (IC50 = 890 nmol/mL, noncompetitive inhibition and BuChE (IC50 = 28 nmol/mL, mixed type inhibition, while the octyl sulfenamide prodrug did not present anti-AChE activity, but exhibited mixed inhibition towards BuChE (IC50 = 184 nmol/mL. Therefore, these two bulkier prodrugs were concluded to be the most selective compounds for BuChE over AChE. In conclusion, it was demonstrated that biguanides present a novel class of inhibitors for AChE and BuChE and encourages further studies of these compounds for developing both selective and nonselective inhibitors of ChEs in the future.

A critical review of cholinesterase inhibitors as a treatment modality in Alzheimer's disease

Science.gov (United States)

S. Schneider, Lon

2000-01-01

Early research into Alzheimer's disease launched the cholinergic hypothesis, based on the correlation between central cholinergic deficiency and clinical measures of cognitive decline. This was epitomized in therapeutic strategies employing a variety of procholinergic agents, of which only the inhibitors of cholinesterase (ChE), the enzyme thai hydrolyzes acetylcholine in the synaptic cleft, have been proven clinically viable. Five such agents are reviewed: tacrine and donepezil, which act at the ionic subsite of acetylcholinesterase (AChE), and rivastigmine, galantamine, and metrifonate, which act at its catalytic esteratic subsite. Despite statistical evidence of efficacy from numerous well-controlled multicenter trials, important clinical utility issues remain outstanding: (i) number-needed-to-treat (NNT) analyses, quantifying the number of patients needing to be treated for one patient to show benefit, find values of 3 to 20; (ii) the pivotal trials themselves were conducted in nonrepreseniative populations, largely comprised of physically healthy outpatients with mildto-moderate Alzheimer's disease and a mean age of 72 years (thereby excluding over 30% of typical Alzheimer patients in State of California-funded clinics), treated for up to 6 months; and (Hi) tolerability is underreported and characterized by a positive correlation between dose, effect and cholinergic side effects - potentially serious adverse events include bradycardia, anorexia, weight loss and myasthenia with respiratory depression. Therapies thus require titration and constant monitoring. Nevertheless, acetylcholinesterase inhibitors (AChEls) constitute the first class of effective agents and are likely to remain so in the continuing absence of viable alternatives. PMID:22033801

Care and education in the Danish Créche

DEFF Research Database (Denmark)

Broström, Stig; Hansen, Ole Henrik

2010-01-01

This article seeks to identify the relation between policy and lived life, for the small child in the Danish crèche. To accomplish this, the article integrates demography, traditions, national curriculum and psychological, educational, and recent developments in research. It is an attempt to reveal...... research articles. It is used in the exploration of meanings of political, social, and cultural phenomena as experienced by the involved individuals themselves, in their natural context. It is a presumption that the child’s development is a consequence of emotional and cognitive stimulation. To outline...... that, it is vital to emphasize the influence that policy causes on educational practice in the crèche, e.g., the conceptualization of education and care....

LA LINGUA FILMATA: "L'UOMO CHE VERRÀ" DI GIORGIO DIRITTI

Directory of Open Access Journals (Sweden)

Marta Idini

2016-02-01

Full Text Available La lingua filmata appare oggi uno dei campi linguistici in cui il dialetto torna ad essere scelta registica e veicolo di nuove istanze comunicative, in stretta relazione con un nuovo modo di intendere e praticare il cinema. Il presente articolo introduce il lettore alla consuetudine cinematografica del dialetto, analizzandone la presenza e le funzioni che gli sono state attribuite nei decenni trascorsi e presenti, e guarda a L’Uomo che verrà quale espressione attuale di una nuova risorgenza dialettale all’interno delle pellicole nostrane. Attraverso un’analisi attenta dei fenomeni vernacolari in esso presenti, l’indagine si sofferma sulle motivazioni e l’efficacia comunicativa cui perviene l’uso del dialetto e si interroga su quale grado di realismo o mimesi linguistica Diritti abbia raggiunto. Language of film: "L’uomo che verrà" by Giorgio DirittiLanguage in films is one of the fields where dialect becomes a choice and a vehicle for new communicative demands, closely related the new way of understanding and practicing the cinema. This article introduces the reader to the use of dialect in films, analyzing the presence and functions that have been attributed to it in the past and present decades, and looks at L’Uomo che verrà as an expression of the new resurgence of dialect in Italian films. Through careful analysis of the vernacular, the paper focuses on the motivations and the communicative effectiveness of the use of dialect and questions the degree of realism or linguistic mimesis that Diritti was able to reach.

Mechanism of soman-induced contractions in canine tracheal smooth muscle. (Reannouncement with new availability information)

Energy Technology Data Exchange (ETDEWEB)

Adler, M.; Moore, D.H.; Filbert, M.G.

1992-12-31

The actions of the irreversible organophosphorus cholinesterase (ChE) inhibitor soman were investigated on canine trachea smooth muscle in vitro. Concentrations of soman > or - 1 nM increased the amplitude and decay of contractions elicited by electric field stimulation. The effect on decay showed a marked dependence on stimulation frequency, undergoing a 2.4-fold increase between 3 and 60 Hz. Soman also potentiated tensions due to bath applied acetylcholine (ACh). Little or no potentiation was observed for contractions elicited by carbamylcholine, an agonist that is not hydrolyzed by ChE. Concentration of soman > or - 3 nM led to the appearance of sustained contractures. These contractures developed with a delayed onset and were well correlated with ChE activity. Alkylation of muscarinic receptors by propylbenzilylcholine mustard antagonized the actions of soman on both spontaneous and electrically-evoked muscle contractions. The results are consistent with a mechanism in which the toxic actions of soman are mediated by accumulation of neurally-released ACh secondary to inhibition of ChE activity. An important factor in this accumulation is suggested to be the buffering effect of the muscarinic receptors on the efflux of ACh from the neuroeffector junction. Tracheal smooth muscle, Cholinesterase inhibitors, Muscarinic receptor, Soman, Organophosphate.

A CheR/CheB fusion protein is involved in cyst cell development and chemotaxis in Azospirillum brasilense Sp7.

Science.gov (United States)

Wu, Lixian; Cui, Yanhua; Hong, Yuanyuan; Chen, Sanfeng

2011-12-20

We here report the sequence and functional analysis of cstB of Azospirillum brasilense Sp7. The predicted cstB contains C-terminal two PAS domains and N-terminal part which has similarity with CheB-CheR fusion protein. cstB mutants had reduced swarming ability compared to that of A. brasilense wild-type strain, implying that cstB was involved in chemotaxis in A. brasilense. A microscopic analysis revealed that cstB mutants developed mature cyst cells more quickly than wild type, indicating that cstB is involved in cyst formation. cstB mutants were affected in colony morphology and the production of exopolysaccharides (EPS) which are essential for A. brasilense cells to differentiate into cyst-like forms. These observations suggested that cstB was a multi-effector involved in cyst development and chemotaxis in A. brasilense. Copyright © 2010 Elsevier GmbH. All rights reserved.

Atividade colinesterásica cerebral e comportamento de ratos após exposição perinatal ao diclorvós Brain cholinesterase activity and the behavior of rats after perinatal exposure to dichlorvos

Directory of Open Access Journals (Sweden)

Jaqueline Pérola de Souza

2006-04-01

Full Text Available O organofosforado diclorvós impregnado em coleiras plásticas é um recurso utilizado em medicina veterinária que visa ao controle de ectoparasitas de cães e gatos. O objetivo deste trabalho foi avaliar os efeitos do uso de coleiras plásticas impregnadas com diclorvós (8,37% em ratas Wistar durante o período de gestação e lactação, como possível fonte de alterações comportamentais e da atividade colinesterásica cerebral dos filhotes. Na desmama, não houve diferença na atividade colinesterásica cerebral entre as mães tratadas com diclorvós e o grupo controle, bem como entre os respectivos filhotes. O tratamento com diclorvós também não influenciou no comportamento geral dos animais, avaliado no campo aberto, nem no nível de ansiedade testado no labirinto em cruz elevado, ambos aos 35 dias pós-natal.The organophosphate dichlorvos impregnated into plastic collars (8.37% is used in veterinary practice as an alternative for the control of ectoparasites in dogs and cats. The aim of this work was to determine the possible toxic effects of these collars in female Wistar rats during pregnancy and lactation, as a possible cause of alterations in brain cholinesterase activity and behavior of offspring. At weaning, there was no difference in brain cholinesterase activity between control and treated dams, nor between their respective offspring as well. The treatment did not affect the general behavior of the offspring, when evaluated in the open field, nor anxiety in the elevated plus-maze, both evaluated on the 35th postnatal day.

Serum cholinesterases are differentially regulated in normal and dystrophin-deficient mutant mice

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Andrea R. Durrant

2012-06-01

Full Text Available The cholinesterases, acetylcholinesterase and butyrylcholinesterase (pseudocholinesterase, are abundant in the nervous system and in other tissues. The role of acetylcholinesterase in terminating transmitter action in the peripheral and central nervous system is well understood. However, both knowledge of the function(s of the cholinesterases in serum, and of their metabolic and endocrine regulation under normal and pathological conditions, is limited. This study investigates acetylcholinesterase and butyrylcholinesterase in sera of dystrophin-deficient mdx mutant mice, an animal model for the human Duchenne muscular dystrophy and in control healthy mice. The data show systematic and differential variations in the concentrations of both enzymes in the sera, and specific changes dictated by alteration of hormonal balance in both healthy and dystrophic mice. While acetylcholinesterase in mdx-sera is elevated, butyrylcholinesterase is markedly diminished, resulting in an overall cholinesterase decrease compared to sera of healthy controls. The androgen testosterone (T is a negative modulator of butyrylcholinesterase, but not of acetylcholinesterase, in male mouse sera. T-removal elevated both butyrylcholinesterase activity and the butyrylcholinesterase/acetylcholinesterase ratio in mdx male sera to values resembling those in healthy control male mice. Mechanisms of regulation of the circulating cholinesterases and their impairment in the dystrophic mice are suggested, and clinical implications for diagnosis and treatment are considered.

Advances toward multifunctional cholinesterase and β-amyloid aggregation inhibitors.

Science.gov (United States)

Panek, Dawid; Wichur, Tomasz; Godyń, Justyna; Pasieka, Anna; Malawska, Barbara

2017-10-01

The emergence of a multitarget design approach in the development of new potential anti-Alzheimer's disease agents has resulted in the discovery of many multifunctional compounds focusing on various targets. Among them the largest group comprises inhibitors of both cholinesterases, with additional anti-β-amyloid aggregation activity. This review describes recent advances in this research area and presents the most interesting compounds reported over a 2-year span (2015-2016). The majority of hybrids possess heterodimeric structures obtained by linking structurally active fragments interacting with different targets. Multipotent cholinesterase inhibitors with β-amyloid antiaggregating activity may additionally possess antioxidative, neuroprotective or metal-chelating properties or less common features such as anti-β-secretase or τ-antiaggregation activity.

Modulation of fusiform cortex activity by cholinesterase inhibition predicts effects on subsequent memory.

Science.gov (United States)

Bentley, P; Driver, J; Dolan, R J

2009-09-01

Cholinergic influences on memory are likely to be expressed at several processing stages, including via well-recognized effects of acetylcholine on stimulus processing during encoding. Since previous studies have shown that cholinesterase inhibition enhances visual extrastriate cortex activity during stimulus encoding, especially under attention-demanding tasks, we tested whether this effect correlates with improved subsequent memory. In a within-subject physostigmine versus placebo design, we measured brain activity with functional magnetic resonance imaging while healthy and mild Alzheimer's disease subjects performed superficial and deep encoding tasks on face (and building) visual stimuli. We explored regions in which physostigmine modulation of face-selective neural responses correlated with physostigmine effects on subsequent recognition performance. In healthy subjects physostigmine led to enhanced later recognition for deep- versus superficially-encoded faces, which correlated across subjects with a physostigmine-induced enhancement of face-selective responses in right fusiform cortex during deep- versus superficial-encoding tasks. In contrast, the Alzheimer's disease group showed neither a depth of processing effect nor restoration of this with physostigmine. Instead, patients showed a task-independent improvement in confident memory with physostigmine, an effect that correlated with enhancements in face-selective (but task-independent) responses in bilateral fusiform cortices. Our results indicate that one mechanism by which cholinesterase inhibitors can improve memory is by enhancing extrastriate cortex stimulus selectivity at encoding, in a manner that for healthy people but not in Alzheimer's disease is dependent upon depth of processing.

A crèche for CERN staff The Staff Association project

CERN Multimedia

Association du personnel

2006-01-01

For many years, the Staff Association has supported the demand for the creation of a crèche for the children of CERN staff. Several studies have been carried out without leading to a concrete plan. The fact that the CERN population is getting younger and the shortage of local facilities have led to a more urgent demand for this type of social service over the past few years. Furthermore, the Equal Opportunities Panel had already recommended that crèche places be made available.

Site-specific and synergistic stimulation of methylation on the bacterial chemotaxis receptor Tsr by serine and CheW

Directory of Open Access Journals (Sweden)

Weis Robert M

2005-03-01

Full Text Available Abstract Background Specific glutamates in the methyl-accepting chemotaxis proteins (MCPs of Escherichia coli are modified during sensory adaptation. Attractants that bind to MCPs are known to increase the rate of receptor modification, as with serine and the serine receptor (Tsr, which contributes to an increase in the steady-state (adapted methylation level. However, MCPs form ternary complexes with two cytoplasmic signaling proteins, the kinase (CheA and an adaptor protein (CheW, but their influences on receptor methylation are unknown. Here, the influence of CheW on the rate of Tsr methylation has been studied to identify contributions to the process of adaptation. Results Methyl group incorporation was measured in a series of membrane samples in which the Tsr molecules were engineered to have one available methyl-accepting glutamate residue (297, 304, 311 or 493. The relative rates at these sites (0.14, 0.05, 0.05 and 1, respectively differed from those found previously for the aspartate receptor (Tar, which was in part due to sequence differences between Tar and Tsr near site four. The addition of CheW generated unexpectedly large and site-specific rate increases, equal to or larger than the increases produced by serine. The increases produced by serine and CheW (added separately were the largest at site one, ~3 and 6-fold, respectively, and the least at site four, no change and ~2-fold, respectively. The rate increases were even larger when serine and CheW were added together, larger than the sums of the increases produced by serine and CheW added separately (except site four. This resulted in substantially larger serine-stimulated increases when CheW was present. Also, CheW enhanced methylation rates when either two or all four sites were available. Conclusion The increase in the rate of receptor methylation upon CheW binding contributes significantly to the ligand specificity and kinetics of sensory adaptation. The synergistic effect of

Che cos'è la vita ?, Scienza e umanesimo

CERN Document Server

Schrödinger, Erwin

1988-01-01

A cento anni dalla nascita di Erwin Schrödinger (Viena 1887), il suo pensiero e il suo lavoro mantengono inalterati la loro attualità, come dimostra la nuova pubblicazione di molti dei suoi testi e i numerosi convegni che gli vengono dedicati.

[Correlation and conversion of plasma cholinesterase activity values using three techniques].

Science.gov (United States)

Carmona-Fonseca, Jaime

2007-07-01

To determine mathematical correlations of three quantitative techniques to measure plasma cholinesterase, using reference values already established for two populations in the department of Antioquia, Colombia. In this descriptive, cross-sectional, prospective study, two independent, representative samples of working adults (18 to 65 years old) were examined. In both samples the adults worked for businesses associated with Colombia's Social Security system. Adults in the two samples had not been exposed to cholinesterase-inhibiting pesticides. The samples were from two neighboring regions of the department of Antioquia: one sample (415 adults) was from the Aburrá Valley, and the other (412 adults) was from Oriente Antioqueño (Eastern Antioquia). Plasma cholinesterase (EC 3.1.1.8) was measured using three quantitative methods: Michel, EQM, and Monotest. Linear regression equations were developed to correlate results of these three techniques. Six simple linear regression equations were defined to show the relationship of three measurement techniques for plasma cholinesterase. There was a moderate correlation of the three techniques (r = 0.686 to 0.771), but it increased (r = 0.744 to 0.811) when 12 (1.5%) outliers were eliminated. Associations among the three techniques were highly significant (P EQM (U/mL) = 0.40773 + 1.8757 (Michel [delta pH/h]); Michel (delta pH/h) = 0.25799 + 0.33871 (EQM [U/mL]); Monotest (U/L) = 462.0 + 4 565.0 (Michel [delta pH/h]); Michel (delta pH/h) = 0.42956 + 0.00012125 (Monotest [U/L]); EQM (U/mL) = 0.75333 + 0.00031056 (Monotest [U/L]); and Monotest (U/L) = 262.0 + 2 118.0 (EQM [U/mL]). The proposed mathematical models allow conversion of cholinesterase activity values using the Michel, EQM, and Monotest techniques. These models can be of assistance in Colombia and other countries where a variety of measurement techniques are used, and where it becomes difficult to compare the results of different studies. Having mathematical models

Organophosphate insecticide poisoning of Canada geese in the Texas panhandle

Science.gov (United States)

White, D.H.; Mitchell, C.A.; Wynn, L.D.; Flickinger, Edward L.; Kolbe, E.J.

1982-01-01

Sixteen hundred waterfowl, mostly Canada Geese, died near Etter, Texas, in late January 1981 from anticholinesterase poisoning. Winter wheat in the area of the die-off had been treated with organophosphate insecticides to control greenbugs. Cholinesterase (ChE) levels in brains of a sample of geese found dead were 75% below normal, enough to account for death (Ludke et al. 1975). The gastrointestinal (G I) tracts of geese found dead were packed with winter wheat; gas chromatography techniques identified parathion and methyl parathion in the GI tract contents. Residues of both chemicals were confirmed by mass spectrometry. We recommend that less toxic materials, such as malathion, be used on grain crops when waterfowl are in the vicinity of treatment.

Altruisti, cooperativi e morali: Perché è più facile esserlo domani che oggi

NARCIS (Netherlands)

Giacomantonio, M.; de Dreu, C.K.W.

2013-01-01

Un portafogli smarrito e ritrovato. Una donazione ad un ente che si occupa di ricerca sulle malattie degenerative. Una tangente non accettata. Un divorzio che si conclude senza il ricorso al tribunale. Alla base di tutti questi eventi vi è la tendenza umana a cooperare, ad essere altruisti e ad

Inwentarz fary chełmińskiej i jej biblioteki z XV wieku

Directory of Open Access Journals (Sweden)

Mateusz Superczyński

2017-07-01

Full Text Available Artykuł niniejszy prezentuje edycję nieznanego szerzej dotychczas inwentarza fary chełmińskiej i wykazu księgozbioru biblioteki farnej z XV w., które znajdują się w księdze miejskiej Chełmna – kopiariuszu przywilejów i dokumentów, założonej przez pisarza Konrada Bitschina w 1431 r. Przekaz źródłowy daje obraz biblioteki fary chełmińskiej jako ośrodka kultury w XV-wiecznym Chełmnie. Pozwala także na porównanie trzech zachowanych spisów księgozbiorów średniowiecznego Chełmna, a więc z klasztoru Franciszkanów z XIII wieku, biblioteki farnej i zrekonstruowanego spisu biblioteki Braci Wspólnego Życia z końca XV stulecia, które pochodzą z różnych okresów i odzwierciedlają przemiany w duchowości, teologii i zainteresowaniach naukowych ówczesnych elit intelektualnych miasta. Podczas gdy księgozbiory biblioteki franciszkanów czy farnej oddają ducha średniowiecznej scholastyki czy nominalizmu, to wydania, które posiadali Bracia Wspólnego Życia, zwiastują nadejście humanizmu. Odnotowane przez pisarza miejskiego tytuły, mimo zniekształceń,pozwalają także na identyfikację i odnalezienie wśród nich fundamentalnych dla średniowiecznej teologii, liturgii, historii i filozofii dzieł.

Anti-cholinesterase activity of the standardized extract of Syzygium aromaticum L.

Science.gov (United States)

Dalai, Manoj K; Bhadra, Santanu; Chaudhary, Sushil K; Bandyopadhyay, Arun; Mukherjee, Pulok K

2014-04-01

Clove (Syzygium aromaticum) is a well-known culinary spice with strong aroma; contains a high amount of oil known as clove oil. The major phyto-constituent of the clove oil is eugenol. Clove and its oil possess various medicinal uses in indigenous medicine as an antiseptic, anti-oxidant, analgesic and neuroprotective properties. Thus, it draws much attention among researchers from pharmaceutical, food and cosmetic industries. The aim of the present study was to determine the anti-cholinesterase activity of the methanol extract of clove, its oil and eugenol. In vitro anti-cholinesterase activity of S. aromaticum was performed by a thin layer chromatography bio autography, 96 well micro titer plate and kinetic methods. Reverse phase high performance liquid chromatography (RP-HPLC) analysis was carried out to identify the biomarker compound eugenol in clove oil. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition study revealed that eugenol possess better inhibition of the enzymes than extract and oil. Clove extract, its oil and eugenol showed better inhibition of AChE than BChE. Polyphenolic compound eugenol was detected through RP-HPLC analysis. The content of eugenol in essential oil was found to be 0.5 μg/ml. Kinetic analysis of the cholinesterase inhibition study of the extract; clove oil and eugenol have shown that they possess mixed type of inhibition for AChE and non-competitive type of inhibition for BChE. These results might be useful in explaining the effect of clove as anti-cholinesterase agent for the management of cognitive ailments like Alzheimer's disease.

Acetyl-cholinesterase Enzyme Inhibitory Effect of Calophyllum species

African Journals Online (AJOL)

Purpose: To search for new acetylcholinesterase enzyme inhibitors from Calopyllum species. Methods: Six stem bark extracts of Calophyllum inophyllum, C. soulattri, C. teysmannii, C. lowii, C. benjaminum and C. javanicum were subjected to anti-cholinesterase analysis against acetylcholinesterase (AChE) enzyme using ...

Correlation between Cholinesterase and Paraoxonase 1 Activities: Case Series of Pesticide Poisoning Subjects

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S Austin Richard

2013-08-01

Full Text Available Introduction: Acute exposure to pesticide due to suicidal poisoning is the most extensive cause of pesticide exposure, compared with all other causes including agricultural or industrial exposure. Organophosphate (OP and carbamate group of pesticides can inhibit acetylcholinesterase; on the other hand, paraoxonase1 can detoxify organophosphate poisoning by hydrolyzing organophosphate metabolites. Methods: We have compared the serum paraoxonase1 status and cholinesterase activity of subjects who attempted to commit suicide by consuming OP pesticide. Cholinesterase and paraoxonase1 activity were measured spectrophotometrically using butyrylthiocholine and phenyl acetate as substrates, respectively. Results: A positive correlation was found between serum paraoxonase1 activity and cholinesterase activity among pesticide consumed subjects. Conclusion: Our results suggest that subjects with higher paraoxonase1 activity may have a better chance of detoxifying the lethal effect of acute organophosphate poisoning.

Il lungo freddo storia di Bruno Pontecorvo, lo scienziato che scelse l'URSS

CERN Document Server

Mafai, Miriam

2012-01-01

Nelle parole della grande giornalista recentemente scomparsa, la documentata narrazione della storia di Bruno Pontecorvo, fisico nucleare di fama mondiale che, nel pieno della Guerra fredda, scelse di abbandonare l'Occidente e di lavorare e vivere nell'Unione Sovietica. Grazie alla capacità della Mafai nel ricostruire gli eventi cruciali della vita di Pontecorvo in un nuovo quadro rivelatore, "Il lungo freddo" non offre solo un'inedita prospettiva sulla drammatica corsa alla bomba atomica - dalle decisive scoperte del Progetto Manhattan alla tragica esplosione di Hiroshima, dalla prima atomica sovietica alla bomba all'idrogeno - ma rappresenta soprattutto la memoria collettiva di una generazione che ha posto la politica al centro delle proprie scelte di vita. E svela i drammi umani di un conflitto che per più di quarant'anni ha diviso il mondo.

A cheZ-Like Gene in Azorhizobium caulinodans Is a Key Gene in the Control of Chemotaxis and Colonization of the Host Plant.

Science.gov (United States)

Liu, Xiaolin; Liu, Wei; Sun, Yu; Xia, Chunlei; Elmerich, Claudine; Xie, Zhihong

2018-02-01

Chemotaxis can provide bacteria with competitive advantages for survival in complex environments. The CheZ chemotaxis protein is a phosphatase, affecting the flagellar motor in Escherichia coli by dephosphorylating the response regulator phosphorylated CheY protein (CheY∼P) responsible for clockwise rotation. A cheZ gene has been found in Azorhizobium caulinodans ORS571, in contrast to other rhizobial species studied so far. The CheZ protein in strain ORS571 has a conserved motif similar to that corresponding to the phosphatase active site in E. coli The construction of a cheZ deletion mutant strain and of cheZ mutant strains carrying a mutation in residues of the putative phosphatase active site showed that strain ORS571 participates in chemotaxis and motility, causing a hyperreversal behavior. In addition, the properties of the cheZ deletion mutant revealed that ORS571 CheZ is involved in other physiological processes, since it displayed increased flocculation, biofilm formation, exopolysaccharide (EPS) production, and host root colonization. In particular, it was observed that the expression of several exp genes, involved in EPS synthesis, was upregulated in the cheZ mutant compared to that in the wild type, suggesting that CheZ negatively controls exp gene expression through an unknown mechanism. It is proposed that CheZ influences the Azorhizobium -plant association by negatively regulating early colonization via the regulation of EPS production. This report established that CheZ in A. caulinodans plays roles in chemotaxis and the symbiotic association with the host plant. IMPORTANCE Chemotaxis allows bacteria to swim toward plant roots and is beneficial to the establishment of various plant-microbe associations. The level of CheY phosphorylation (CheY∼P) is central to the chemotaxis signal transduction. The mechanism of the signal termination of CheY∼P remains poorly characterized among Alphaproteobacteria , except for Sinorhizobium meliloti , which

Cholinesterase catalyzed hydrolysis of O-acyl derivatives of serotonin

International Nuclear Information System (INIS)

Makhaeva, G.F.; Suvorov, N.N.; Ginodman, L.N.; Antonov, V.K.; AN SSSR, Moscow. Inst. Bioorganicheskoj Khimii)

1977-01-01

Hydrolysis of O acyl serotonin derivatives containing the residues of monocarbon dicarbon and amino acids under the effect of horse serum butyryl cholinesterase and bull erythrocytic acetylcholinesterase has been studied. It has been established, that acetylcholinesterase hydrolizes O acetylserotonin only; butyrylcholinesterase hydrolizes all the compounds investigated, except for 5,5'-terephthaloildioxytriptamine. The kinetic parameters of hydrolysis were determined. O acyl serotonin derivatives turned out good substrates of butylrylcholinesterase; serotonin and 5.5'-terephtaloildioxytriptamine are effective competitine inhibitors of the enzyme. Estimating of resistance of O acyl serotonin derivatines to blood cholinesterase effect under physiological conditions shows that the compounds investigated with the exception of 5,5'-terephthaloildioxytriptamine must be quickly hydrolyzed under butyrylcholinesterase action. 5,5'-terephthaloildioxytriptamine is suggested as a radioprotective preparation with the prolonged effect, which agrees with the biological test results

Dual inhibitors of cholinesterases and monoamine oxidases for Alzheimer's disease.

Science.gov (United States)

Knez, Damijan; Sova, Matej; Košak, Urban; Gobec, Stanislav

2017-05-01

Accumulating evidence indicates a solid relationship between several enzymes and Alzheimer's disease. Cholinesterases and monoamine oxidases are closely associated with the disease symptomatology and progression and have been tackled simultaneously using several multifunctional ligands. This design strategy offers great chances to alter the course of Alzheimer's disease, in addition to alleviation of the symptoms. More than 15 years of research has led to the identification of various dual cholinesterase/monoamine oxidase inhibitors, while some showing positive outcomes in clinical trials, thus giving rise to additional research efforts in the field. The aim of this review is to provide an update on the novel dual inhibitors identified recently and to shed light on their therapeutic potential.

Proline-Based Carbamates as Cholinesterase Inhibitors

Czech Academy of Sciences Publication Activity Database

Pizova, H.; Havelková, M.; Štěpánková, Š.; Bak, A.; Kauerová, T.; Kozik, V.; Oravec, Michal; Imramovský, A.; Kollár, P.; Bobáľ, P.; Jampílek, J.

2017-01-01

Roč. 22, č. 11 (2017), č. článku 1969. ISSN 1420-3049 R&D Projects: GA MŠk(CZ) LO1415; GA MŠk(CZ) EF16_013/0001609 Institutional support: RVO:86652079 Keywords : proline * carbamates * in vitro cholinesterase inhibition * in vitro cytotoxicity assay * CoMSA * IVE-PLS * molecular docking study Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 2.861, year: 2016

Serum Acetyl Cholinesterase as a Biomarker of Arsenic Induced Neurotoxicity in Sprague-Dawley Rats

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Paul B. Tchounwou

2005-04-01

Full Text Available Arsenic is an environmental toxicant, and one of the major mechanisms by which it exerts its toxic effect is through an impairment of cellular respiration by inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Recent studies have pointed out that arsenic toxicity is associated with the formation of reactive oxygen species, which may cause severe injury/damage to the nervous system. The main objective of this study was to conduct biochemical analysis to determine the effect of arsenic trioxide on the activity of acetyl cholinesterase; a critical important nervous system enzyme that hydrolyzes the neurotransmitter acetylcholine. Four groups of six male rats each weighing an average 60 + 2 g were used in this study. Arsenic trioxide was intraperitoneally administered to the rats at the doses of 5, 10, 15, 20mg/kg body weight (BW, one dose per 24 hour given for five days. A control group was also made of 6 animals injected with distilled water without chemical. Following anaesthesia, blood specimens were immediately collected using heparinized syringes, and acetyl cholinesterase detection and quantification were performed in serum samples by spectrophotometry. Arsenic trioxide exposure significantly decreased the activity of cholinesterase in the Sprague-Dawley rats. Acetyl cholinesterase activities of 6895 + 822, 5697 + 468, 5069 + 624, 4054 + 980, and 3158 + 648 U/L were recorded for 0, 5, 10, 15, and 20 mg/kg, respectively; indicating a gradual decrease in acetyl cholinesterase activity with increasing doses of arsenic. These findings indicate that acetyl

[The activity of blood cholinesterase in rats exposed to dimethypo after drug intervention].

Science.gov (United States)

Wan, Weiguo; Xu, Mailing; Zou, Hejian; Lu, Ailing; Shen, Xinyu; Chen, Yuming

2002-12-01

To investigate the activity of ChE in rats poisoned by dimehypo and then treated with pralidoxime methylchloride or unithiol. Rats were divided into control group (dimehypo); intervention groups [dimehypo plus pralidoxime methylchloride or dimehypo plus unithiol (sodium dimercaptopropanesulphonate)]. Rats were dosed with 4 different doses of dimehypo: 1/16, 1/8, 1/4 and 1/2 of LD50 respectively(the LD50 of dimehypo is 342 mg/kg). After being poisoned with dimehypo orally, rats were immediately injected intramuscularly with pralidoxime methylchloride or unithiol. The activity of ChE in blood was detected before and 1/2, 1, 2, 4 and 24 h after poisoning in dimehypo and intervention groups. The ChE activity of four dose subgroups at 1 h after poisoning were (1.04 +/- 0.21), (0.84 +/- 0.12), (0.71 +/- 0.12), (0.66 +/- 0.07) U/ml respectively; the ChE activity of pralidoxime methylchloride intervention groups were (1.01 +/- 0.18), (1.17 +/- 0.11), (1.01 +/- 0.04), (1.03 +/- 0.12) U/ml respectively; and the ChE activity of unithiol intervention groups were (1.15 +/- 0.15), (1.26 +/- 0.27), (1.08 +/- 0.08), (1.04 +/- 0.12) U/ml respectively. The inhibited ChE in blood was recovered by either treatment with pyraldoxime methylchloride or unithiol. These two drugs had similar effects of recovering the activity of ChE(P > 0.05), but at higher doses(1/4 and 1/2 of LD50) the effects of both were not so good. Pralidoxime methylchloride and unithiol could partly recover the activity of ChE inhibited by dimehypo.

Natural gas prices in Italy. Tariffs geographical distribution; Metano. Paese che vai, prezzo che trovi

Energy Technology Data Exchange (ETDEWEB)

Marrocchelli, A. [ENEA, Rome (Italy). Centro Ricerche Casaccia

2000-11-01

The annual report on services and activity carries at some evaluations of data concerned the natural gas market: total consumption, costs and prices in Italy and comparative evaluations with other european countries. [Italian] La relazione annuale sullo stato dei servizi e sull'attivita' svolta, presentata dal Presidente dell'Autorita' per l'energia elettrica e il gas, porta ad alcune considerazioni sui dati che riguardano il mercato del gas naturale: i consumi totali, i costi e i prezzi in Italia, il confronto con i costi e i prezzi praticati negli altri paesi europei.

An Age-Dependent Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for the Organophosphorus Insecticide Chlorpyrifos in the Preweanling Rat

Energy Technology Data Exchange (ETDEWEB)

Timchalk, Chuck; Kousba, Ahmed A.; Poet, Torka S.

2007-08-01

Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. In the current study, a modified physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent changes in CYP450, PON-1, and tissue ChE levels for rats was developed. In this model, age was used as a dependent function to estimate body weight which was then used to allometrically scale both metabolism and tissue ChE levels. Model simulations suggest that preweanling rats are particularly sensitive to CPF toxicity, with levels of CPF-oxon in blood and brain disproportionately increasing, relative to the response in adult rats. This age-dependent non-linear increase in CPF-oxon concentration may potentially result from the depletion of non-target B-esterases, and a lower PON-1 metabolic capacity in younger animals. These results indicate that the PBPK/PD model behaves consistently with the general understanding of CPF toxicity, pharmacokinetics and tissue ChE inhibition in neonatal and adult rats. Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children.

Pesticide Exposure and Cholinesterase Levels in Migrant Farm Workers in Thailand.

Science.gov (United States)

Thetkathuek, Anamai; Yenjai, Pornthip; Jaidee, Wanlop; Jaidee, Patchana; Sriprapat, Poonsak

2017-01-01

In this study, we examined the effects of pesticides in migrant farm workers from Cambodia after workplace exposure on fruit plantations in eastern Thailand. We studied 891 migrant farm workers employed on pineapple, durian, and rambutan plantations in Thailand. Data were collected via a detailed questionnaire survey and measurements of serum cholinesterase level (SChE). The majority of subjects was male (57.7%), with an average age of 30.3 years. Most subjects (76.8%) were moderately aware of good industrial hygiene practices. SChE level was divided into four groups based on the results. Only 4.4% had normal levels of cholinesterase activity, 20.5% had slightly reduced levels, 58.5% had markedly reduced levels and were "at risk," and 16.6% who had highest levels of cholinesterase inhibition were deemed to be in an "unsafe" range. SChE was classified into two groups, SChE value of 87.5 was "normal" and 39 acres, use a backpack sprayer, or have a low level of compliance with accepted industrial hygiene practices. These three classes of workers are at increased risk of chemical exposures and developing acute or chronic illness from pesticide exposures.

Distinct Domains of CheA Confer Unique Functions in Chemotaxis and Cell Length in Azospirillum brasilense Sp7.

Science.gov (United States)

Gullett, Jessica M; Bible, Amber; Alexandre, Gladys

2017-07-01

Chemotaxis is the movement of cells in response to gradients of diverse chemical cues. Motile bacteria utilize a conserved chemotaxis signal transduction system to bias their motility and navigate through a gradient. A central regulator of chemotaxis is the histidine kinase CheA. This cytoplasmic protein interacts with membrane-bound receptors, which assemble into large polar arrays, to propagate the signal. In the alphaproteobacterium Azospirillum brasilense , Che1 controls transient increases in swimming speed during chemotaxis, but it also biases the cell length at division. However, the exact underlying molecular mechanisms for Che1-dependent control of multiple cellular behaviors are not known. Here, we identify specific domains of the CheA1 histidine kinase implicated in modulating each of these functions. We show that CheA1 is produced in two isoforms: a membrane-anchored isoform produced as a fusion with a conserved seven-transmembrane domain of unknown function (TMX) at the N terminus and a soluble isoform similar to prototypical CheA. Site-directed and deletion mutagenesis combined with behavioral assays confirm the role of CheA1 in chemotaxis and implicate the TMX domain in mediating changes in cell length. Fluorescence microscopy further reveals that the membrane-anchored isoform is distributed around the cell surface while the soluble isoform localizes at the cell poles. Together, the data provide a mechanism for the role of Che1 in controlling multiple unrelated cellular behaviors via acquisition of a new domain in CheA1 and production of distinct functional isoforms. IMPORTANCE Chemotaxis provides a significant competitive advantage to bacteria in the environment, and this function has been transferred laterally multiple times, with evidence of functional divergence in different genomic contexts. The molecular principles that underlie functional diversification of chemotaxis in various genomic contexts are unknown. Here, we provide a molecular

Crèche and School: Open Day on Saturday, 3 March

CERN Multimedia

EVE et École

2018-01-01

Open Day at Crèche and School of the CERN Staff Association Are you considering enrolling your child to the Crèche and School of the CERN Staff Association? If you work at CERN, then this event is for you: come visit the school and meet the Management on Saturday 3 March 2018 from 10 to 12 am It will be our pleasure to present to you our structure, its projects and premises, and answer any questions you may have. Please sign up for one of the two sessions via Doodle before Wednesday 28 February 2018: https://doodle.com/poll/3qvrb6m73pktqbft

The history of cholinesterase reactivation: hydroxylamine and pyridinium aldoximes.

Science.gov (United States)

Petroianu, G A

2012-10-01

Hydroxylamine (NH2OH) the substance which will turn out to be of importance to those interested in the treatment of organophosporus cholinesterase inhibitor exposure, was synthesized by Wilhem Clemens Lossen in 1865 while working in Halle as an assistant in the laboratory of Wilhelm Heinrich Heintz. The Lossen synthesis generated hydroxylamine in aqueous solution. Anhydrous hydroxylamine was prepared almost simultaneously by Lobry de Bruyn and Crismer (1891). Using hydroxylamine as a starting point Meyer synthesized aldoximes and ketoximes (1897). Lange, a PhD student of Ladenburg, isolated 2-methyl-pyridine (alpha-picoline). Some fifty years later Wilson, working in the laboratory of Nachmansohn, demonstrated the ability of hydroxylamine to reactivate cholinesterase inhibited by organophosphates. Finally Wilson and Ginsburg using 2-methyl-pyridine as a starting point synthesized the first pyridinium aldoxime reactivator of clinical relevance, pralidoxime (1955).

Storie ‘vere’ ed eroine dei romanzi. Rappresentare la Somalia in 'Ilaria Alpi. La ragazza che voleva raccontare l’inferno' e 'Non dirmi che hai paura'

Directory of Open Access Journals (Sweden)

Simone Brioni

2016-09-01

Full Text Available ‘True’ Stories and Heroines in Novels: The Representation of Somalia in Ilaria Alpi: The Young Woman Who Wanted to Narrate Hell and Don’t Tell Me You Are AfraidThis article analyses Gigliola Alvisi’s Ilaria Alpi: La ragazza che voleva raccontare l’inferno [Ilaria Alpi: The Young Woman Who Wanted to Narrate the Hell] (2014 and Giuseppe Catozzella’s Non dirmi che hai paura [Don’t Tell Me You Are Afraid] (2014, two novels that deal with two recent events in Somali and Italian history, the killing of the journalist Ilaria Alpi in Mogadishu in 1994 and the death of Samia Yosuf Omar while she was trying to reach the Italian shores from Libya by boat. Alvisi’s text is analysed in comparison with other fictional and journalistic representations of Ilaria Alpi, while Non dirmi che hai paura is examined through what Catozzella considers the two constitutive dimensions of the novel: documentation and identification. Drawing on Stefano Jossa’s reflections on the construction of literary heroes, the article challenges Alvisi’s and Catozzella’s claims that they represent ‘true stories’. The article also argues that the main characters of these literary works are portrayed as heroines and role models for the emancipation of Muslim women.

Effect Of Nicotine And Tobacco Consumption On Brain Acetyl ...

African Journals Online (AJOL)

The effect of nicotine and tobacco consumption on brain acetyl cholinesterase and serum alkaline phosphatase in rats was studied. Rats were divided into three groups and the first group was fed rat chow and water ad libitum and an oral administration of 2ml of 0.1%(v/v) nicotine per 100g body weight of rats per day.

Evaluation of Candidate Genes for cholinesterase Activity in Farmworkers Exposed to organophosphorous Pesticides-Association of SNPs in BCHE

Science.gov (United States)

Background: Organophosphate pesticides act as cholinesterase inhibitors, and as such may give rise to potential neurological effects. Cholinesterase activity is a useful, indirect measurement of pesticide exposure, especially in high-risk individuals such as farmworkers. To und...

The new "Jardin de Capucine" crèche brings a breath of fresh air for young CERN parents

CERN Multimedia

HR Department

2011-01-01

On 19 January 2011, CERN's Director-General, Rolf Heuer, signed an agreement with the company "Le Jardin de Zébulon" for the provision of 40 places at the "Jardin de Capucine", a new private crèche due to open this autumn.   In 2008, the "Jardin de Zébulon", a private bilingual crèche for children aged 1 to 4, was opened by Ariane Boucheron at the Technoparc industrial estate in Saint-Genis Pouilly (France). The following year, the number of places was increased from 20 to 37 to meet demand. The "Jardin de Zébulon" has taken in a number of children of CERN personnel ever since it was created. With no let-up in the demand for new crèche places, Ariane Boucher is currently engaged in the construction of a new centre, the "Jardin de Capucine", next-door to the existing crèche. Forty places at the new crèche will...

Simplified methods for in vivo measurement of acetylcholinesterase activity in rodent brain

International Nuclear Information System (INIS)

Kilbourn, Michael R.; Sherman, Phillip S.; Snyder, Scott E.

1999-01-01

Simplified methods for in vivo studies of acetylcholinesterase (AChE) activity in rodent brain were evaluated using N-[ 11 C]methylpiperidinyl propionate ([ 11 C]PMP) as an enzyme substrate. Regional mouse brain distributions were determined at 1 min (representing initial brain uptake) and 30 min (representing trapped product) after intravenous [ 11 C]PMP administration. Single time point tissue concentrations (percent injected dose/gram at 30 min), tissue concentration ratios (striatum/cerebellum and striatum/cortex ratios at 30 min), and regional tissue retention fractions (defined as percent injected dose 30 min/percent injected dose 1 min) were evaluated as measures of AChE enzymatic activity in mouse brain. Studies were carried out in control animals and after dosing with phenserine, a selective centrally active AChE inhibitor; neostigmine, a peripheral cholinesterase inhibitor; and a combination of the two drugs. In control and phenserine-treated animals, absolute tissue concentrations and regional retention fractions provide good measures of dose-dependent inhibition of brain AChE; tissue concentration ratios, however, provide erroneous conclusions. Peripheral inhibition of cholinesterases, which changes the blood pharmacokinetics of the radiotracer, diminishes the sensitivity of all measures to detect changes in central inhibition of the enzyme. We conclude that certain simple measures of AChE hydrolysis rates for [ 11 C]PMP are suitable for studies where alterations of the peripheral blood metabolism of the tracer are kept to a minimum

Synthesis and biological evaluation of lycorine derivatives as dual inhibitors of human acetylcholinesterase and butyrylcholinesterase

Directory of Open Access Journals (Sweden)

Wang Yue-Hu

2012-09-01

Full Text Available Abstract Background Alzheimer’s disease (AD is a neurologically degenerative disorder that affects more than 20 million people worldwide. The selective butyrylcholinesterase (BChE inhibitors and bivalent cholinesterase (ChE inhibitors represent new treatments for AD. Findings A series of lycorine derivatives (1–10 were synthesized and evaluated for anti-cholinesterase activity. Result showed that the novel compound 2-O-tert-butyldimethylsilyl-1-O-(methylthiomethyllycorine (7 was a dual inhibitor of human acetylcholinesterase (hAChE and butyrylcholinesterase (hBChE with IC50 values of 11.40 ± 0.66 μM and 4.17 ± 0.29 μM, respectively. The structure-activity relationships indicated that (i the 1-O-(methylthiomethyl substituent in lycorine was better than the 1-O-acetyl group for the inhibition of cholinesterase; (ii the acylated or etherified derivatives of lycorine and lycorin-2-one were more potent against hBChE than hAChE; and (iii the oxidation of lycorine at C-2 decreases the activity. Conclusion Acylated or etherified derivatives of lycorine are potential dual inhibitors of hBChE and hAChE. Hence, further study on the modification of lycorine for ChE inhibition is necessary.

Structural insights into cholinesterases inhibition by harmane β-carbolinium derivatives: a kinetics-molecular modeling approach.

Science.gov (United States)

Torres, Juliana M; Lira, Aline F; Silva, Daniel R; Guzzo, Lucas M; Sant'Anna, Carlos M R; Kümmerle, Arthur E; Rumjanek, Victor M

2012-09-01

The natural indole alkaloids, the β-carbolines, are often associated with cholinesterase inhibition, especially their quaternary salts, which frequently have higher activity than the free bases. Due to lack of information explaining this fact in the literature, the cholinesterase inhibition by the natural product harmane and its two β-carbolinium synthetic derivative salts (N-methyl and N-ethyl) was explored, together with a combination of kinetics and a molecular modeling approach. The results, mainly for the β-carbolinium salts, demonstrated a noncompetitive inhibition profile, ruling out previous findings which associated cholinesterase inhibition by β-carbolinium salts to a possible mimicking of the choline moiety of the natural substrate, acetylcholine. Molecular modeling studies corroborate this kind of inhibition through analyses of inhibitor/enzyme and inhibitor/substrate/enzyme complexes of both enzymes. Copyright © 2012 Elsevier Ltd. All rights reserved.

La Pubblica Amministrazione in uno scenario che cambia

Directory of Open Access Journals (Sweden)

Renzo Carlucci

2009-03-01

Full Text Available Questo numero, mirato alle implicazioni dell'utilizzo del dato territoriale nel contesto delle PA, le Pubbliche Amministrazioni, si arricchisce di un contenuto ulteriore, particolarmente spaziale; GEOmedia esce infatti in coincidenza con una manifestazione che possiamo considerare la vetrina mediterranea privilegiata per la promozione culturale, scientifica e commerciale delle istituzioni e del segmento dell’industria aerospaziale europea ed italiana.

Efficient Computation of Sparse Matrix Functions for Large-Scale Electronic Structure Calculations: The CheSS Library.

Science.gov (United States)

Mohr, Stephan; Dawson, William; Wagner, Michael; Caliste, Damien; Nakajima, Takahito; Genovese, Luigi

2017-10-10

We present CheSS, the "Chebyshev Sparse Solvers" library, which has been designed to solve typical problems arising in large-scale electronic structure calculations using localized basis sets. The library is based on a flexible and efficient expansion in terms of Chebyshev polynomials and presently features the calculation of the density matrix, the calculation of matrix powers for arbitrary powers, and the extraction of eigenvalues in a selected interval. CheSS is able to exploit the sparsity of the matrices and scales linearly with respect to the number of nonzero entries, making it well-suited for large-scale calculations. The approach is particularly adapted for setups leading to small spectral widths of the involved matrices and outperforms alternative methods in this regime. By coupling CheSS to the DFT code BigDFT, we show that such a favorable setup is indeed possible in practice. In addition, the approach based on Chebyshev polynomials can be massively parallelized, and CheSS exhibits excellent scaling up to thousands of cores even for relatively small matrix sizes.

Molecular modeling and biological evaluation of 2-N,N-dimethylaminecyclohexyl 1-N‧,N‧-dimethylcarbamate isomers and their methylsulfate salts as cholinesterases inhibitors

Science.gov (United States)

Bocca, Cleverson C.; Rittner, Roberto; Höehr, Nelci F.; Pinheiro, Glaucia M. S.; Abiko, Layara A.; Basso, Ernani A.

2010-11-01

This work presents a detailed theoretical and experimental study on the inhibitory properties of 2- N,N-dimethylaminecyclohexyl 1- N',N'-dimethylcarbamate isomers and their methylsulfate salts against the cholinesterases enzymes. The in vitro inhibition test performed by the Ellman's method showed that the salt form compounds were more active than the neutral ones in cholinesterases inhibition. The trans salt showed good selectivity towards the inhibition of erythrocyte cholinesterase with a maximum limit around 90% and 55% for the plasma cholinesterase inhibition. Molecular modeling, docking and experimental results performed in this study showed to be important initial steps toward the development of a novel pharmaceuticals in the fight against Alzheimer's disease.

Simplified methods for in vivo measurement of acetylcholinesterase activity in rodent brain

Energy Technology Data Exchange (ETDEWEB)

Kilbourn, Michael R. E-mail: mkilbour@umich.edu; Sherman, Phillip S.; Snyder, Scott E

1999-07-01

Simplified methods for in vivo studies of acetylcholinesterase (AChE) activity in rodent brain were evaluated using N-[{sup 11}C]methylpiperidinyl propionate ([{sup 11}C]PMP) as an enzyme substrate. Regional mouse brain distributions were determined at 1 min (representing initial brain uptake) and 30 min (representing trapped product) after intravenous [{sup 11}C]PMP administration. Single time point tissue concentrations (percent injected dose/gram at 30 min), tissue concentration ratios (striatum/cerebellum and striatum/cortex ratios at 30 min), and regional tissue retention fractions (defined as percent injected dose 30 min/percent injected dose 1 min) were evaluated as measures of AChE enzymatic activity in mouse brain. Studies were carried out in control animals and after dosing with phenserine, a selective centrally active AChE inhibitor; neostigmine, a peripheral cholinesterase inhibitor; and a combination of the two drugs. In control and phenserine-treated animals, absolute tissue concentrations and regional retention fractions provide good measures of dose-dependent inhibition of brain AChE; tissue concentration ratios, however, provide erroneous conclusions. Peripheral inhibition of cholinesterases, which changes the blood pharmacokinetics of the radiotracer, diminishes the sensitivity of all measures to detect changes in central inhibition of the enzyme. We conclude that certain simple measures of AChE hydrolysis rates for [{sup 11}C]PMP are suitable for studies where alterations of the peripheral blood metabolism of the tracer are kept to a minimum.

La nascita imperfetta delle cose la grande corsa alla particella di Dio e la nuova fisica che cambierà il mondo

CERN Document Server

AUTHOR|(CDS)2068901

2016-01-01

In quel preciso momento, un centesimo di miliardesimo di secondo dopo il Big Bang, si è deciso il nostro destino. In un universo in cui materia e antimateria si equivalevano, e che quindi avrebbe potuto, in ogni istante, tornare a essere pura energia, può essere bastata una leggerissima preferenza del bosone di Higgs per la materia anziché per l'antimateria ed ecco che si è prodotto il mondo che abbiamo sotto gli occhi. "Ecco qua il minuscolo difetto, la sottile imperfezione da cui è nato tutto. Un'anomalia che dà origine a un universo che può evolvere per miliardi di anni." Se tutto nasce da lì, dobbiamo capire in ogni dettaglio quel momento cruciale, ricostruirlo fotogramma per fotogramma, al rallentatore e da diverse angolature. Per questo al Cern di Ginevra è stato realizzato Lhc, l'acceleratore di particelle più potente del mondo, il posto più simile al primo istante di vita dell'universo che l'uomo sia stato in grado di costruire. Per questo da anni i migliori fisici del mondo lavorano giorno...

[How aliphatic alcohols and ph affect reactional capability of the horse blood serum cholinesterase at its interaction with organophosphorus inhibitors].

Science.gov (United States)

Basova, N E; Kormilitsin, B N; Perchenok, A Iu; Rozengart, E V; Saakov, V S; Suvorov, A A

2013-01-01

There was studied action of aliphatic alcohols (ethanol, propanol, isopropanol, n-butanol, isobutanol, secbutanol, tretbetanol) and pH on various kinds of reactional capability the serum cholinesterase. At the alcohols-affected inhibition of the cholinesterase hydrolytic activity, the determining role was played not the total number carbon atoms in the alcohol molecule, but by the "effective length" of the carbohydrate chain. The fact that the presence of alcohols did not affect parameters of the reverse cholinesterase inhibition with onium ions tetramethylammonium and choline allows suggesting the absence of effect solvents on specific acetylcholine sorption in the enzyme active center. With aid of two rows of hydrophobic organophosphorus inhibitors (OPI), we have managed to estimate both the degree and the character itself of the modifying action of alcohols and pH on the process of irreversible inhibition of serum cholinesterase.

HUBUNGAN ANTARA PERILAKU DALAM PENGELOLAAN PESTISIDA DENGAN AKTIVITAS ENZIM CHOLINESTERASE DARAH PADA PETANI CABE DI DESA SANTANA MEKAR KECAMATAN CISAYONG KABUPATEN TASIKMALAYA

Directory of Open Access Journals (Sweden)

Ai Sukmawati

2012-11-01

Full Text Available A study on use pesticide was conducted in Santana Mekar village, Tasikmalaya regency in June 2003. The aim of this study was to find out the relationship between knowledge, attitude and practice of pesticide use and blood cholinesterase enzyme activities. The study used survey method and cross sectional approach. The result showed that 34.5% from 61 respondents have normal blood cholinesterase enzyme activity. Most of the respondents have good knowledge, attitude and practice on using pesticides. Rank spearman correlation analysis shows that a positive relation was found between knowledge, attitude and practice on using pesticides with blood cholinesterase enzyme activity (p=0.001, a=0.1 .   Keywords : behavior, pesticide, blood cholinesterase enzyme activity

Cognitive and affective changes in mild to moderate Alzheimer's disease patients undergoing switch of cholinesterase inhibitors: a 6-month observational study.

Directory of Open Access Journals (Sweden)

Gianfranco Spalletta

Full Text Available Patients with Alzheimer's disease after an initial response to cholinesterase inhibitors may complain a later lack of efficacy. This, in association with incident neuropsychiatric symptoms, may worsen patient quality of life. Thus, the switch to another cholinesterase inhibitor could represent a valid therapeutic strategy. The aim of this study was to investigate the effectiveness of the switch from one to another cholinesterase inhibitor on cognitive and affective symptoms in mild to moderate Alzheimer disease patients. Four hundred twenty-three subjects were included from the EVOLUTION study, an observational, longitudinal, multicentre study conducted on Alzheimer disease patients who switched to different cholinesterase inhibitor due either to lack/loss of efficacy or response, reduced tolerability or poor compliance. All patients underwent cognitive and neuropsychiatric assessments, carried out before the switch (baseline, and at 3 and 6-month follow-up. A significant effect of the different switch types was found on Mini-Mental State Examination score during time, with best effectiveness on mild Alzheimer's disease patients switching from oral cholinesterase inhibitors to rivastigmine patch. Depressive symptoms, when measured using continuous Neuropsychiatric Inventory values, decreased significantly, while apathy symptoms remained stable over the 6 months after the switch. However, frequency of both depression and apathy, when measured categorically using Neuropsychiatric Inventory cut-off scores, did not change significantly during time. In mild to moderate Alzheimer disease patients with loss of efficacy and tolerability during cholinesterase inhibitor treatment, the switch to another cholinesterase inhibitor may represent an important option for slowing cognitive deterioration. The evidence of apathy stabilization and the positive tendency of depressive symptom improvement should definitively be confirmed in double-blind controlled

Measurement of K-27, an oxime-type cholinesterase reactivator by high-performance liquid chromatography with electrochemical detection from different biological samples.

Science.gov (United States)

Gyenge, Melinda; Kalász, Huba; Petroianu, George A; Laufer, Rudolf; Kuca, Kamil; Tekes, Kornélia

2007-08-17

K-27 is a bisquaternary asymmetric pyridinium aldoxime-type cholinesterase reactivator of use in the treatment of poisoning with organophosphorous esterase inhibitors. A sensitive, simple and reliable reverse-phase high-performance liquid chromatographic method with electrochemical detection was developed for the measurement of K-27 concentrations in rat brain, cerebrospinal fluid, serum and urine samples. Male Wistar rats were treated intramuscularly with K-27 and the samples were collected 60 min later. Separation was carried out on an octadecyl silica stationary phase and a disodium phosphate solution (pH 3.7) containing citric acid, octane sulphonic acid and acetonitrile served as mobile phase. Measurements were carried out at 30 degrees C at E(ox) 0.65 V. The calibration curve was linear through the range of 10-250 ng/mL. Accuracy, precision and the limit of detection calculated were satisfactory according to internationally accepted criteria. Limit of quantitation was 10 ng/mL. The method developed is reliable and sensitive enough for monitoring K-27 levels from different biological samples including as little as 10 microL of cerebrospinal fluid. The method--with slight modification in the composition of the mobile phase--can be used to measure a wide range of other related pyridinium aldoxime-type cholinesterase reactivators.

TLC-bioautographic evaluation of in vitro anti-tyrosinase and anti-cholinesterase potentials of sandalwood oil.

Science.gov (United States)

Misra, Biswapriya B; Dey, Satyahari

2013-02-01

Sandalwood oil, rich in sesquiterpenoid alcohols, has been used in traditional medicinal systems as a relaxant and coolant. Besides, sandalwood oil is used as an ingredient in numerous skin fairness enhancing cosmetics. However, there is no available information on biological activities that relate to the above applications. Hence, the anti-tyrosinase and anti-cholinesterase potentials of sandalwood oil were probed by both TLC-bioautographic and colorimetric methods. Results obtained from colorimetric assays indicated that sandalwood oil is a potent inhibitor of tyrosinase (IC50 = 171 microg mL(-1)) and cholinesterases (IC50 = 4.8-58 microg mL(-1)), in comparison with the positive controls used in the assays, kojic acid and physostigmine, respectively. The TLC-bioautographic assays indicated that alpha-santalol, the major constituent of the oil, is a strong inhibitor of both tyrosinase and cholinesterase. These in vitro results indicate that there is a great potential of this essential oil for use in the treatment of Alzheimer's disease, as well as in skin-care.

Synthesis and bioevaluation of new tacrine-cinnamic acid hybrids as cholinesterase inhibitors against Alzheimer's disease.

Science.gov (United States)

Chen, Yao; Zhu, Jie; Mo, Jun; Yang, Hongyu; Jiang, Xueyang; Lin, Hongzhi; Gu, Kai; Pei, Yuqiong; Wu, Liang; Tan, Renxiang; Hou, Jing; Chen, Jingyi; Lv, Yang; Bian, Yaoyao; Sun, Haopeng

2018-12-01

Small molecule cholinesterases inhibitor (ChEI) provides an effective therapeutic strategy to treat Alzheimer's disease (AD). Currently, the discovery of new ChEI with multi-target effect is still of great importance. Herein, we report the synthesis, structure-activity relationship study and biological evaluation of a series of tacrine-cinnamic acid hybrids as new ChEIs. All target compounds are evaluated for their in vitro cholinesterase inhibitory activities. The representatives which show potent activity on cholinesterase, are evaluated for the amyloid β-protein self-aggregation inhibition and in vivo assays. The optimal compound 19, 27, and 30 (human AChE IC 50  = 10.2 ± 1.2, 16.5 ± 1.7, and 15.3 ± 1.8 nM, respectively) show good performance in ameliorating the scopolamine-induced cognition impairment and preliminary safety in hepatotoxicity evaluation. These compounds deserve further evaluation for the development of new therapeutic agents against AD.

Resorcinol-, catechol- and saligenin-based bronchodilating β2-agonists as inhibitors of human cholinesterase activity.

Science.gov (United States)

Bosak, Anita; Knežević, Anamarija; Gazić Smilović, Ivana; Šinko, Goran; Kovarik, Zrinka

2017-12-01

We investigated the influence of bronchodilating β2-agonists on the activity of human acetylcholinesterase (AChE) and usual, atypical and fluoride-resistant butyrylcholinesterase (BChE). We determined the inhibition potency of racemate and enantiomers of fenoterol as a resorcinol derivative, isoetharine and epinephrine as catechol derivatives and salbutamol and salmeterol as saligenin derivatives. All of the tested compounds reversibly inhibited cholinesterases with K i constants ranging from 9.4 μM to 6.4 mM and had the highest inhibition potency towards usual BChE, but generally none of the cholinesterases displayed any stereoselectivity. Kinetic and docking results revealed that the inhibition potency of the studied compounds could be related to the size of the hydroxyaminoethyl chain on the benzene ring. The additional π-π interaction of salmeterol's benzene ring and Trp286 and hydrogen bond with His447 probably enhanced inhibition by salmeterol which was singled out as the most potent inhibitor of all the cholinesterases.

Attenuation of MPTP-induced dopaminergic neurotoxicity by TV3326, a cholinesterase-monoamine oxidase inhibitor.

Science.gov (United States)

Sagi, Yotam; Weinstock, Marta; Youdim, Moussa B H

2003-07-01

(R)-[(N-propargyl-(3R) aminoindan-5-yl) ethyl methyl carbamate] (TV3326) is a novel cholinesterase and brain-selective monoamine oxidase (MAO)-A/-B inhibitor. It was developed for the treatment of dementia co-morbid with extra pyramidal disorders (parkinsonism), and depression. On chronic treatment in mice it attenuated striatal dopamine depletion induced by MPTP and prevented the reduction in striatal tyrosine hydroxylase activity, like selective B and non-selective MAO inhibitors. TV3326 preferentially inhibits MAO-B in the striatum and hippocampus, and the degree of MAO-B inhibition correlates with the prevention of MPTP-induced dopamine depletion. Complete inhibition of MAO-B is not necessary for full protection from MPTP neurotoxicity. Unlike that seen after treatment with other MAO-A and -B inhibitors, recovery of striatal and hippocampal MAO-A and -B activities from inhibition by TV3326 did not show first-order kinetics. This has been attributed to the generation of a number of metabolites by TV3326 that cause differential inhibition of these enzymes. Inhibition of brain MAO-A and -B by TV3326 resulted in significant elevations of dopamine, noradrenaline and serotonin in the striatum and hippocampus. This may explain its antidepressant-like activity, resembling that of moclobemide in the forced-swim test in rats.

Demonstrating the Open Data Repository's Data Publisher: The CheMin Database

Science.gov (United States)

Stone, N.; Lafuente, B.; Bristow, T.; Pires, A.; Keller, R. M.; Downs, R. T.; Blake, D.; Dateo, C. E.; Fonda, M.

2018-04-01

The Open Data Repository's Data Publisher aims to provide an easy-to-use software tool that will allow researchers to create and publish database templates and related data. The CheMin Database developed using this framework is shown as an example.

Accumulation of phenolic compounds in in vitro cultures and wild plants of Lavandula viridis L'Hér and their antioxidant and anti-cholinesterase potential.

Science.gov (United States)

Costa, Patrícia; Gonçalves, Sandra; Valentão, Patrícia; Andrade, Paula B; Romano, Anabela

2013-07-01

In this study, we evaluated the phenolic profile, antioxidant and anti-cholinesterase potential of different extracts from wild plants and in vitro cultures of Lavandula viridis L'Hér. The HPLC-DAD analysis allowed the identification and quantification of 3-O-caffeoylquinic, 4-O-caffeoylquinic, 5-O-caffeoylquinic and rosmarinic acids, and luteolin and pinocembrin. Water/ethanol extract from in vitro cultures contained the highest amount of the identified phenolic compounds (51652.92 mg/kg). To investigate the antioxidant activity we used Trolox equivalent antioxidant capacity, oxygen radical absorbance capacity, Fe(2+) chelation activity and the inhibition of Fe(2+)-induced lipid peroxidation in mouse brain homogenates (in vitro). Overall, all the extracts from both wild plants and in vitro cultures exhibited ability to scavenge free radicals, to chelate Fe(2+) and to protect against lipid peroxidation. In addition, the extracts from L. viridis were active in inhibiting both acetylcholinesterase and butyrylcholinesterase (Ellman's method). Our findings suggest that L. viridis in vitro cultures represent a promising alternative for the production of active metabolites with antioxidant and anti-cholinesterase activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Design, synthesis, pharmacological evaluation, QSAR analysis, molecular modeling and ADMET of novel donepezil-indolyl hybrids as multipotent cholinesterase/monoamine oxidase inhibitors for the potential treatment of Alzheimer's disease.

Science.gov (United States)

Bautista-Aguilera, Oscar M; Esteban, Gerard; Bolea, Irene; Nikolic, Katarina; Agbaba, Danica; Moraleda, Ignacio; Iriepa, Isabel; Samadi, Abdelouahid; Soriano, Elena; Unzeta, Mercedes; Marco-Contelles, José

2014-03-21

The design, synthesis, and pharmacological evaluation of donepezil-indolyl based amines 7-10, amides 12-16, and carboxylic acid derivatives 5 and 11, as multipotent ASS234 analogs, able to inhibit simultaneously cholinesterase (ChE) and monoamine oxidase (MAO) enzymes for the potential treatment of Alzheimer's disease (AD), is reported. Theoretical studies using 3D-Quantitative Structure-Activity Relationship (3D-QSAR) was used to define 3D-pharmacophores for inhibition of MAO A/B, AChE, and BuChE enzymes. We found that, in general, and for the same substituent, amines are more potent ChE inhibitors (see compounds 12, 13 versus 7 and 8) or equipotent (see compounds 14, 15 versus 9 and 10) than the corresponding amides, showing a clear EeAChE inhibition selectivity. For the MAO inhibition, amides were not active, and among the amines, compound 14 was totally MAO A selective, while amines 15 and 16 were quite MAO A selective. Carboxylic acid derivatives 5 and 11 showed a multipotent moderate selective profile as EeACE and MAO A inhibitors. Propargylamine 15 [N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)prop-2-yn-1-amine] resulted in the most potent hMAO A (IC50 = 5.5 ± 1.4 nM) and moderately potent hMAO B (IC50 = 150 ± 31 nM), EeAChE (IC50 = 190 ± 10 nM), and eqBuChE (IC50 = 830 ± 160 nM) inhibitor. However, the analogous N-allyl and the N-morpholine derivatives 16 and 14 deserve also attention as they show an attractive multipotent profile. To sum up, donepezil-indolyl hybrid 15 is a promising drug for further development for the potential prevention and treatment of AD. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

LE SOLUTRÉEN ANCIEN EN ARDÈCHE (FRANCE: UNE RÉVISION CRITIQUE DES INDUSTRIES LITHIQUES

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Sophie Guegan

2013-11-01

Full Text Available S’inscrivant dans un travail de Doctorat sur les peuplements des deux rives de la vallée du Rhône au Maximum Glaciaire, cet article propose un état des connaissances sur la phase ancienne du Solutréen en Ardèche (rive droite du Rhône, donnant lieu à une révision critique des industries lithiques s’y rapportant. En effet, depuis les travaux de P.E.L. Smith et J. Combier, et plus récemment le travail d’A. Barbiero consacré aux pointes à face plance et pointes à cran d’une collection ancienne à la Baume d’Oullins (Gard-Ardèche, France, aucun réexamen global n’avait été entrepris. Trois gisements de référence pour cette phase ancienne, ont ainsi été sélectionnés: les grottes d’Oullins (Gard-Ardèche, France, de Chabot (Gard, France et de Granouly (Ardèche, France. Nous présentons ici les réslutats préliminaires à cette étude. En premier lieu, une approche typologique a été menée principalement autour de la pointe à face plane, objet emblématique de cette phase, permettant d’en préciser les principaux caractères. Dans un deuxième temps, une approche technologique a permis de confirmer l’homogénéité dans les choix techniques des Solutréens entre l’Ardèche et les régions du Sud-Ouest et du Bassin Parisien. Enfin, une étude des matières premières, a révélé pour l’heure des choix économiques étonnants pour le contexte paléo-climatique, avec des déplacements vers le nords et un franchissement du Rhône.In the frame of a doctoral dissertation on the Late Glacial Maximum occupations of both sides of the Rhône valley, this paper presents a state of the art and a critical reappraisal of the lithic assemblages from the early phases of the Solutrean in Ardeche (right bank of the Rhône river. Indeed, since the works of P.E.L. Smith and J. Combier, except the work of A. Barbiero, on the unifacial leaf-points and shouldered points from Baume d'Oullins, no complete study of these

[Cholinesterase inhibitors for treating dementia. Review].

Science.gov (United States)

Kremer, Janus

2010-01-01

Alzheimer's disease is the most common form of dementia seen in the clinical practice. The principal risk factor is aging. There is not currently any available curative medication. However, there a family of drugs call the cholinesterase inhibitors (donepezile, galantamine and rivastigmine) the enhances cholinergic activity in the CNS. Also, memantine is available is a NMDA receptor modulator. A new transdermal way of administration is available now for rivastigmine. The rivastigmines patches are now a rational alternative focusing in getting more tolerance, better blood levels of the drug and compliance to treatment in Alzheimer's disease patients.

New evidences of neurotoxicity of aroclor 1254 in mice brain: potential of coenzyme q10 in abating the detrimental outcomes

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Anuradha Majumdar

2014-03-01

Full Text Available Objectives The present subacute study was designed to evaluate the effect of coenzyme Q 10 (CoQ10 in the 28 days aroclor 1254 exposure induced oxidative stress in mice brain. Methods Biochemical estimations of brain lipid peroxidation (LPO, reduced glutathione (GSH, and activities of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx and acetyl cholinesterase (AChE, and histopathological investigations of brain tissue were carried out. Results Oral exposure of aroclor 1254 (5 mg/kg led to significant decrease in levels of GSH, and activities of SOD, CAT, GPx, and AChE, and increase in LPO. These aberrations were restored by CoQ10 (10 mg/kg, intraperitoneal injection [IP]. This protection offered was comparable to that of L-deprenyl (1 mg/kg, IP which served as a reference standard. Conclusions Aroclor 1254 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in the brains of Swiss albino mice. Supplementation of CoQ10 abrogates these deleterious effects of aroclor 1254. CoQ10 also apparently enhanced acetyl cholinesterase activity which reflects its influence on the cholinergic system.

Molecular Interaction and Cellular Location of RecA and CheW Proteins in Salmonella enterica during SOS Response and Their Implication in Swarming.

Science.gov (United States)

Irazoki, Oihane; Aranda, Jesús; Zimmermann, Timo; Campoy, Susana; Barbé, Jordi

2016-01-01

In addition to its role in DNA damage repair and recombination, the RecA protein, through its interaction with CheW, is involved in swarming motility, a form of flagella-dependent movement across surfaces. In order to better understand how SOS response modulates swarming, in this work the location of RecA and CheW proteins within the swarming cells has been studied by using super-resolution microscopy. Further, and after in silico docking studies, the specific RecA and CheW regions associated with the RecA-CheW interaction have also been confirmed by site-directed mutagenesis and immunoprecipitation techniques. Our results point out that the CheW distribution changes, from the cell poles to foci distributed in a helical pattern along the cell axis when SOS response is activated or RecA protein is overexpressed. In this situation, the CheW presents the same subcellular location as that of RecA, pointing out that the previously described RecA storage structures may be modulators of swarming motility. Data reported herein not only confirmed that the RecA-CheW pair is essential for swarming motility but it is directly involved in the CheW distribution change associated to SOS response activation. A model explaining not only the mechanism by which DNA damage modulates swarming but also how both the lack and the excess of RecA protein impair this motility is proposed.

Molecular interaction and cellular location of RecA and CheW proteins in Salmonella enterica during SOS response and their implication in swarming

Directory of Open Access Journals (Sweden)

Oihane Irazoki

2016-10-01

Full Text Available In addition to its role in DNA damage repair and recombination, the RecA protein, through its interaction with CheW, is involved in swarming motility, a form of flagella-dependent movement across surfaces. In order to better understand how SOS response modulates swarming, in this work the location of RecA and CheW proteins within the swarming cells has been studied by using super-resolution microscopy. Further, and after in silico docking studies, the specific RecA and CheW regions associated with the RecA-CheW interaction have also been confirmed by site-directed mutagenesis and immunoprecipitation techniques. Our results point out that the CheW distribution changes, from the cell poles to foci distributed in a helical pattern along the cell axis when SOS response is activated or RecA protein is overexpressed. In this situation, the CheW presents the same subcellular location as that of RecA, pointing out that the previously described RecA storage structures may be modulators of swarming motility. Data reported herein not only confirmed that the RecA-CheW pair is essential for swarming motility but it is directly involved in the CheW distribution change associated to SOS response activation. A model explaining not only the mechanism by which DNA damage modulates swarming but also how both the lack and the excess of RecA protein impair this motility is proposed.

CheShift-2 resolves a local inconsistency between two X-ray crystal structures

International Nuclear Information System (INIS)

Vila, Jorge A.; Sue, Shih-Che; Fraser, James S.; Scheraga, Harold A.; Dyson, H. Jane

2012-01-01

Since chemical shifts provide important and relatively accessible information about protein structure in solution, a Web server, CheShift-2, was developed for structure interrogation, based on a quantum mechanics database of 13 C α chemical shifts. We report the application of CheShift-2 to a local inconsistency between two X-ray crystal structures (PDB IDs 1IKN and 1NFI) of the complex between the p65/p50 heterodimer of NFκB and its inhibitor IκBα. The availability of NMR resonance assignments that included the region of the inconsistency provided an opportunity for independent validation of the CheShift-2 server. Application of the server showed that the 13 C α chemical shifts measured for the Gly270-Pro281 sequence close to the C-terminus of IκBα were unequivocally consistent with the backbone structure modeled in the 1IKN structure, and were inconsistent with the 1NFI structure. Previous NOE measurements had demonstrated that the position of a tryptophan ring in the region immediately N-terminal in this region was not consistent with either structure. Subsequent recalculation of the local structure in this region, based on the electron density of the deposited structure factors for 1IKN, confirmed that the local backbone structure was best modeled by 1IKN, but that the rotamer of Trp258 is consistent with the 1NFI structure, including the presence of a hydrogen bond between the ring NεH of Trp258 and the backbone carbonyl group of Gln278. The consensus between all of these measures suggests that the CheShift-2 server operates well under circumstances in which backbone chemical shifts are available but where local plasticity may render X-ray structural data ambiguous.

The Pseudomonas aeruginosa chemotaxis methyltransferase CheR1 impacts on bacterial surface sampling.

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Juliane Schmidt

Full Text Available The characterization of factors contributing to the formation and development of surface-associated bacterial communities known as biofilms has become an area of intense interest since biofilms have a major impact on human health, the environment and industry. Various studies have demonstrated that motility, including swimming, swarming and twitching, seems to play an important role in the surface colonization and establishment of structured biofilms. Thereby, the impact of chemotaxis on biofilm formation has been less intensively studied. Pseudomonas aeruginosa has a very complex chemosensory system with two Che systems implicated in flagella-mediated motility. In this study, we demonstrate that the chemotaxis protein CheR1 is a methyltransferase that binds S-adenosylmethionine and transfers a methyl group from this methyl donor to the chemoreceptor PctA, an activity which can be stimulated by the attractant serine but not by glutamine. We furthermore demonstrate that CheR1 does not only play a role in flagella-mediated chemotaxis but that its activity is essential for the formation and maintenance of bacterial biofilm structures. We propose a model in which motility and chemotaxis impact on initial attachment processes, dispersion and reattachment and increase the efficiency and frequency of surface sampling in P. aeruginosa.

Rivastigmine alleviates experimentally induced colitis in mice and rats by acting at central and peripheral sites to modulate immune responses.

Directory of Open Access Journals (Sweden)

Helena Shifrin

Full Text Available The cholinergic anti-inflammatory system and α7 nicotinic receptors in macrophages have been proposed to play a role in neuroimmunomodulation and in the etiology of ulcerative colitis. We investigated the ability of a cholinesterase (ChE inhibitor rivastigmine, to improve the pathology of ulcerative colitis by increasing the concentration of extracellular acetylcholine in the brain and periphery. In combination with carbachol (10 µM, rivastigmine (1 µM significantly decreased the release of nitric oxide, TNF-α, IL-1β and IL-6 from lipopolysaccharide-activated RAW 264.7 macrophages and this effect was abolished by α7 nicotinic receptor blockade by bungarotoxin. Rivastigmine (1 mg/kg but not (0.5 mg/kg, injected subcutaneously once daily in BALB/c mice with colitis induced by 4% dextran sodium sulphate (DSS, reduced the disease activity index (DAI by 60% and damage to colon structure. Rivastigmine (1 mg/kg also reduced myeloperoxidase activity and IL-6 by >60%, and the infiltration of CD11b expressing cells by 80%. These effects were accompanied by significantly greater ChE inhibition in cortex, brain stem, plasma and colon than that after 0.5 mg/kg. Co-administration of rivastigmine (1 mg/kg with the muscarinic antagonist scopolamine significantly increased the number of CD11b expressing cells in the colon but did not change DAI compared to those treated with rivastigmine alone. Rivastigmine 1 and 2 mg given rectally to rats with colitis induced by rectal administration of 30 mg dintrobezene sulfonic acid (DNBS also caused a dose related reduction in ChE activity in blood and colon, the number of ulcers and area of ulceration, levels of TNF-α and in MPO activity. The study revealed that the ChE inhibitor rivastigmine is able to reduce gastro-intestinal inflammation by actions at various sites at which it preserves ACh. These include ACh released from vagal nerve endings that activates alpha7 nicotinic receptors on circulating macrophages

Quantitative estimation of cholinesterase-specific drug metabolism of carbamate inhibitors provided by the analysis of the area under the inhibition-time curve.

Science.gov (United States)

Zhou, Huimin; Xiao, Qiaoling; Tan, Wen; Zhan, Yiyi; Pistolozzi, Marco

2017-09-10

Several molecules containing carbamate groups are metabolized by cholinesterases. This metabolism includes a time-dependent catalytic step which temporary inhibits the enzymes. In this paper we demonstrate that the analysis of the area under the inhibition versus time curve (AUIC) can be used to obtain a quantitative estimation of the amount of carbamate metabolized by the enzyme. (R)-bambuterol monocarbamate and plasma butyrylcholinesterase were used as model carbamate-cholinesterase system. The inhibition of different concentrations of the enzyme was monitored for 5h upon incubation with different concentrations of carbamate and the resulting AUICs were analyzed. The amount of carbamate metabolized could be estimated with cholinesterases in a selected compartment in which the cholinesterase is confined (e.g. in vitro solutions, tissues or body fluids), either in vitro or in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

The comparison of lipid profiling in mouse brain and liver after starvation and a high-fat diet: A medical systems biology approach

NARCIS (Netherlands)

Ginneken, V.J.T. van; Verheij, E.; Hekman, M.; Greef, J. van der; Feskens, E.J.M.; Poelmann, R.E.

2011-01-01

We investigated with LC-MS techniques, measuring approximately 109 lipid compounds, in mouse brain and liver tissue after 48 hours of starvation and a High-Fat Diet if brain and liver lipid composition changed. We measured Cholesterolesters (ChE), Lysophosphatidyl-cholines (LPC), Phosphatidylcholine

Structural studies of conformational changes of proteins upon phosphorylation: Structures of activated CheY, CheY-N16-FliM complex, and AAA ⁺ ATPase domain of NtrC1 in both inactive and active states

Energy Technology Data Exchange (ETDEWEB)

Lee, Seok-Yong [Univ. of California, Berkeley, CA (United States)

2003-04-10

Protein phosphorylation is a general mechanism for signal transduction as well as regulation of cellular function. Unlike phosphorylation in eukaryotic systems that uses Ser/Thr for the sites of modification, two-component signal transduction systems, which are prevalent in bacteria, archea, and lower eukaryotes, use an aspartate as the site of phosphorylation. Two-component systems comprise a histidine kinase and a receiver domain. The conformational change of the receiver domain upon phosphorylation leads to signal transfer to the downstream target, a process that had not been understood well at the molecular level. The transient nature of the phospho-Asp bond had made structural studies difficult. The discovery of an excellent analogue for acylphosphate, BeF₃^-, enabled structural study of activated receiver domains. The structure of activated Chemotaxis protein Y (CheY) was determined both by NMR spectroscopy and X-ray crystallography. These structures revealed the molecular basis of the conformational change that is coupled to phosphorylation. Phosphorylation of the conserved Asp residue in the active site allows hydrogen bonding of the T87 Oγ to phospho-aspartate, which in turn leads to the rotation of Y106 into the ''in'' position (termed Y-T coupling). The structure of activated CheY complexed with the 16 N-terminal residues of FliM (N16-FliM), its target, was also determined by X-ray crystallography and confirmed the proposed mechanism of activation (Y-T coupling). First, N16-FliM binds to the region on CheY that undergoes a significant conformational change. Second, the ''in'' position of Y106 presents a better binding surface for FliM because the sidechain of Y106 in the inactive form of CheY (''out'' position) sterically interferes with binding of N16-FliM. In addition to confirmation of Y-T coupling, the structure of the activated CheY-N16-FliM complex suggested that the

Inhibition, recovery and oxime-induced reactivation of muscle esterases following chlorpyrifos exposure in the earthworm Lumbricus terrestris

International Nuclear Information System (INIS)

Collange, B.; Wheelock, C.E.; Rault, M.; Mazzia, C.; Capowiez, Y.; Sanchez-Hernandez, J.C.

2010-01-01

Assessment of wildlife exposure to organophosphorus (OP) pesticides generally involves the measurement of cholinesterase (ChE) inhibition, and complementary biomarkers (or related endpoints) are rarely included. Herein, we investigated the time course inhibition and recovery of ChE and carboxylesterase (CE) activities in the earthworm Lumbricus terrestris exposed to chlorpyrifos, and the ability of oximes to reactivate the phosphorylated ChE activity. Results indicated that these esterase activities are a suitable multibiomarker scheme for monitoring OP exposure due to their high sensitivity to OP inhibition and slow recovery to full activity levels following pesticide exposure. Moreover, oximes reactivated the inhibited ChE activity of the earthworms exposed to 12 and 48 mg kg -1 chlorpyrifos during the first week following pesticide exposure. This methodology is useful for providing evidence for OP-mediated ChE inhibition in individuals with a short history of OP exposure (≤1 week); resulting a valuable approach for assessing multiple OP exposure episodes in the field. - Esterase inhibition combined with oxime reactivation methods is a suitable approach for monitoring organophosphate contamination

Inhibition, recovery and oxime-induced reactivation of muscle esterases following chlorpyrifos exposure in the earthworm Lumbricus terrestris

Energy Technology Data Exchange (ETDEWEB)

Collange, B. [Universite d' Avignon et des Pays de Vaucluse, UMR 406 Abeilles et Environnement, Site AGROPARC, F-84914, Avignon Cede 09 (France); Wheelock, C.E. [Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77, Stockholm (Sweden); Rault, M.; Mazzia, C. [Universite d' Avignon et des Pays de Vaucluse, UMR 406 Abeilles et Environnement, Site AGROPARC, F-84914, Avignon Cede 09 (France); Capowiez, Y. [INRA, Unite PSH, Site AGROPARC, F-84914 Avignon Cedex 09 (France); Sanchez-Hernandez, J.C., E-mail: juancarlos.sanchez@uclm.e [Laboratory of Ecotoxicology, Faculty of Environmental Science, University of Castilla-La Mancha, Avda. Carlos III s/n, 45071, Toledo (Spain)

2010-06-15

Assessment of wildlife exposure to organophosphorus (OP) pesticides generally involves the measurement of cholinesterase (ChE) inhibition, and complementary biomarkers (or related endpoints) are rarely included. Herein, we investigated the time course inhibition and recovery of ChE and carboxylesterase (CE) activities in the earthworm Lumbricus terrestris exposed to chlorpyrifos, and the ability of oximes to reactivate the phosphorylated ChE activity. Results indicated that these esterase activities are a suitable multibiomarker scheme for monitoring OP exposure due to their high sensitivity to OP inhibition and slow recovery to full activity levels following pesticide exposure. Moreover, oximes reactivated the inhibited ChE activity of the earthworms exposed to 12 and 48 mg kg{sup -1} chlorpyrifos during the first week following pesticide exposure. This methodology is useful for providing evidence for OP-mediated ChE inhibition in individuals with a short history of OP exposure (<=1 week); resulting a valuable approach for assessing multiple OP exposure episodes in the field. - Esterase inhibition combined with oxime reactivation methods is a suitable approach for monitoring organophosphate contamination

Influence of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference in rats.

Science.gov (United States)

Gawel, Kinga; Labuz, Krzysztof; Jenda, Malgorzata; Silberring, Jerzy; Kotlinska, Jolanta H

2014-07-15

The influence of systemic administration of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference (CPP) was examined in rats. Additionally, this study aimed to compare the effects of donepezil, which selectively inhibits acetylcholinesterase, and rivastigmine, which inhibits both acetylcholinesterase and butyrylcholinesterase on morphine reward. Morphine-induced CPP (unbiased method) was induced by four injections of morphine (5 mg/kg, i.p.). Donepezil (0.5, 1, and 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5, and 1 mg/kg, i.p.) were given 20 min before morphine during conditioning phase and 20 min before the expression or reinstatement of morphine-induced CPP. Our results indicated that both inhibitors of cholinesterase attenuated the acquisition and expression of morphine CPP. The results were more significant after rivastigmine due to a broader inhibitory spectrum of this drug. Moreover, donepezil (1 mg/kg) and rivastigmine (0.5 mg/kg) attenuated the morphine CPP reinstated by priming injection of 5mg/kg morphine. These properties of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist but not scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. All effects of cholinesterase inhibitors were observed at the doses that had no effects on locomotor activity of animals. Our results suggest beneficial role of cholinesterase inhibitors in reduction of morphine reward and morphine-induced seeking behavior. Finally, we found that the efficacy of cholinesterase inhibitors in attenuating reinstatement of morphine CPP provoked by priming injection may be due to stimulation of nicotinic acetylcholine receptors. Copyright © 2014 Elsevier B.V. All rights reserved.

The Effect of Diazinon on Cholinesterase Activity in Plasma and Erythrocytes of Male and Female Rats and the Protective Role of Vitamin E

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F. Rahimi Anbarkeh

2015-01-01

Full Text Available Introduction & Objective: Diazinon (DZN is an organophosphate insecticide that one of the mechanisms of toxicity is the inhibition of cholinesterase. The aim of the present study was to evaluate the effects of diazinon on cholinesterase activity in blood serum and erythrocytes of male and female rats and to assess the protective role of vitamin E. Materials & Methods: In this experimental study, 60 adult wistar rats including 30 male and 30 female rats were selected and divided into 5 groups (n = 6: control group (without any intervention, sham group (received only pure olive oil daily, experimental group 1 (DZN daily, 60 mg/kg, experimental group 2 (received DZN+ vitamin E daily, with the same dose and experimental group 3(received vitamin E daily 200 mg/kg. Diazinon and solvent were injected intraperitoneally and vitamin E was given by gavage. After 2 weeks 3 ml blood was taken from the heart tissue, and titrimetric and Ellman’s method respectively were used for serum and erythrocyte cholinesterases activity assay. Results: In both genders, due to administration of diazinon, we observed significant reduction in serum and erythrocytes cholinesterase activity. The use of vitamin E increased serum and erythrocytes cholinesterase activity in experimental group 2 of female rats but inhibition in erythrocyte and serum cholinesterase activity was not recovered in experimental group 2 of male rats. Conclusion: According to a further reduction of these enzymes activity in female rats with the use of diazinon, it can be concluded that female rats are more sensitive than male rats and it seems that vitamin E as an antioxidants has a protective effect on cholinesterase activity and reduces the toxicity of DZN. (Sci J Hamadan Univ Med Sci 2015; 21 (4:294-303

X-Ray Diffraction on Mars: Scientific Discoveries Made by the CheMin Instrument

Science.gov (United States)

Rampe, E. B.; Blake, D. F.; Ming, D. W.; Bristow, T. F.

2017-01-01

The Mars Science Laboratory Curiosity landed in Gale crater in August 2012 with the goal to identify and characterize habitable environments on Mars. Curiosity has been studying a series of sedimentary rocks primarily deposited in fluviolacustrine environments approximately 3.5 Ga. Minerals in the rocks and soils on Mars can help place further constraints on these ancient aqueous environments, including pH, salinity, and relative duration of liquid water. The Chemistry and Mineralogy (CheMin) X-ray diffraction and X-ray fluorescence instrument on Curiosity uses a Co X-ray source and charge-coupled device detector in transmission geometry to collect 2D Debye-Scherrer ring patterns of the less than 150 micron size fraction of drilled rock powders or scooped sediments. With an angular range of approximately 2.52deg 20 and a 20 resolution of approximately 0.3deg, mineral abundances can be quantified with a detection limit of approximately 1-2 wt. %. CheMin has returned quantitative mineral abundances from 16 mudstone, sandstone, and aeolian sand samples so far. The mineralogy of these samples is incredibly diverse, suggesting a variety of depositional and diagenetic environments and different source regions for the sediments. Results from CheMin have been essential for reconstructing the geologic history of Gale crater and addressing the question of habitability on ancient Mars.

Sulle ipotesi che stanno alla base della geometria e altri scritti scientifici e filosofici

CERN Document Server

Riemann, Bernhard

1994-01-01

Il volume raccoglie, oltre al testo della lezione del 1854 che dà il titolo all'opera, alcuni scritti di carattere scientifico e filosofico di Riemann. A saggi di argomento scientifico si affiancano scritti di argomento più direttamente metodologico. La concezione della scienza che ci viene offerta da questi scritti è assai significativa del personaggio e della sua epoca. Per Riemann la matematica non è un mero strumento esteriore da applicare, appunto dall'esterno, ai fenomeni. Al contrario, essa consente di spingersi con il rigore necessario oltre alla superficie dei fenomeni e di penetrare sempre più a fondo nella realtà, nell'ottica di un sistema unitario e quasi metafisico del sapere scientifico.

Cloning, overexpression, purification, crystallization and preliminary X-ray analysis of CheY3, a response regulator that directly interacts with the flagellar ‘switch complex’ in Vibrio cholerae

International Nuclear Information System (INIS)

Khamrui, Susmita; Biswas, Maitree; Sen, Udayaditya; Dasgupta, Jhimli

2010-01-01

A chemotaxis response regulator CheY3 from V. cholerae has been cloned, overexpressed, purified and crystallized. The crystals of CheY3 diffracted to 1.86 Å resolution. Vibrio cholerae is the aetiological agent of the severe diarrhoeal disease cholera. This highly motile organism uses the processes of motility and chemotaxis to travel and colonize the intestinal epithelium. Chemotaxis in V. cholerae is far more complex than that in Escherichia coli or Salmonella typhimurium, with multiple paralogues of various chemotaxis genes. In contrast to the single copy of the chemotaxis response-regulator protein CheY in E. coli, V. cholerae contains four CheYs (CheY1–CheY4), of which CheY3 is primarily responsible for interacting with the flagellar motor protein FliM, which is one of the major constituents of the ‘switch complex’ in the flagellar motor. This interaction is the key step that controls flagellar rotation in response to environmental stimuli. CheY3 has been cloned, overexpressed and purified by Ni–NTA affinity chromatography followed by gel filtration. Crystals of CheY3 were grown in space group R3, with a calculated Matthews coefficient of 2.33 Å 3 Da −1 (47% solvent content) assuming the presence of one molecule per asymmetric unit

Crew Health Care System (CHeCS) Design Research, Documentations, and Evaluations

Science.gov (United States)

CLement, Bethany M.

2011-01-01

The Crew Health Care System (CHeCS) is a group within the Space Life Science Directorate (SLSD) that focuses on the overall health of astronauts by reinforcing the three divisions - the Environmental Maintenance System (EMS), the Countermeasures System (CMS), and the Health Maintenance System (HMS). This internship provided opportunity to gain knowledge, experience, and skills in CHeCS engineering and operations tasks. Various and differing tasks allowed for occasions to work independently, network to get things done, and show leadership abilities. Specific exercises included reviewing hardware certification, operations, and documentation within the ongoing Med Kit Redesign (MKR) project, and learning, writing, and working various common pieces of paperwork used in the engineering and design process. Another project focused on the distribution of various pieces of hardware to off-site research facilities with an interest in space flight health care. The main focus of this internship, though, was on a broad and encompassing understanding of the engineering process as time was spent looking at each individual step in a variety of settings and tasks.

Finally a crèche at CERN, thanks to the Staff Association

CERN Multimedia

Staff Association

2013-01-01

Setting up at CERN a collective structure to mind children younger than two years, a so-called “crèche”, has been discussed at least since the early 1990s. Then, in February 2001, the Equal Opportunities Advisory Panel produced a memo to the Director of Administration in which it “invites the CERN Management to re-consider the possibility of creating a crèche at CERN”. As a result an ad hoc task force (“Bethléem”) was set up, which based its work on an informal questionnaire sent to CERN families with small children. Its study came up with some relevant parameters for “should CERN Management intend to undertake a minimal effort toward solving the crèche problem for its staff members”. Nothing was undertaken at that time. In the framework of the 2005 five yearly review “Working Group 6: Crèche” made another study of public and private  cr&a...

The structure and dynamic properties of the complete histidine phosphotransfer domain of the chemotaxis specific histidine autokinase CheA from Thermotoga maritima

International Nuclear Information System (INIS)

Vu, Anh; Hamel, Damon J.; Zhou Hongjun; Dahlquist, Frederick W.

2011-01-01

The bacterial histidine autokinase CheA contains a histidine phosphotransfer (Hpt) domain that accepts a phosphate from the catalytic domain and donates the phosphate to either target response regulator protein, CheY or CheB. The Hpt domain forms a helix-bundle structure with a conserved four-helix bundle motif and a variable fifth helix. Observation of two nearly equally populated conformations in the crystal structure of a Hpt domain fragment of CheA from Thermotoga maritima containing only the first four helices suggests more mobility in a tightly packed helix bundle structure than previously thought. In order to examine how the structures of Hpt domain homologs may differ from each other particularly in the conformation of the last helix, and whether an alternative conformation exists in the intact Hpt domain in solution, we have solved a high-resolution, solution structure of the CheA Hpt from T. maritima and characterized the backbone dynamics of this protein. The structure contains a four-helix bundle characteristic of histidine phosphotransfer domains. The position and orientation of the fifth helix resembles those in known Hpt domain crystal and solution structures in other histidine kinases. The alternative conformation that was reported in the crystal structure of the CheA Hpt from T. maritima missing the fifth helix is not detected in the solution structure, suggesting a role for the fifth helix in providing stabilizing forces to the overall structure.

Effects of Cholinesterase Inhibitors in Parkinson's Disease Dementia : A Review of Clinical Data

NARCIS (Netherlands)

van Laar, Teus; De Deyn, Peter Paul; Aarsland, Dag; Barone, Paolo; Galvin, James E.

2011-01-01

Aims: Cognitive impairment and dementia are common features of Parkinson's disease (PD). Patients with Parkinson's disease dementia (PDD) often have significant cholinergic defects, which may be treated with cholinesterase inhibitors (ChEIs). The objective of this review was to consider available

Potentially hazardous substances in surface waters. II. Cholinesterase inhibitors in Dutch surface waters

NARCIS (Netherlands)

Greve, P.A.; Freudenthal, J.; Wit, S.L.

1972-01-01

Several analytical methods were employed to determine the concentrations of cholinesterase inhibitors in several Dutch surface waters. An Auto-Analyzer method was used for screening purposes; thin-layer chromatography and gas-liquid chromatography-mass spectrometry were used for identification and

El Che - más que médico

Directory of Open Access Journals (Sweden)

Natalia I. Osorio Curbelo

2015-12-01

Full Text Available Revolucionario, dirigente político, comandante guerrillero, intelectual y médico.  Uno de los íconos del siglo XX.  Nació en Rosario, Argentina, el 14 de junio de 1928. En 1938, con apenas 10 años, el padre le enseñó a jugar Ajedrez en el transcurso del año, deporte que no dejaría de practicar nunca más y lo estudiaría por siempre. En 1939 supo de la existencia de Cuba, pues teniendo 11 años, cuando vivía en Alta Gracia, en Buenos Aires se desarrollaba la VII Olimpiada de Ajedrez y el más conocido de los ajedrecistas cubanos José Raúl Capablanca, obtuvo la medalla de Oro en el primer tablero, convirtiéndose en noticia mundial. La gran pasión por el juego ciencia  se puso de manifiesto durante toda su vida, jugó Ajedrez cuando estaba viajando en un avión, cuando  estuvo detenido en alguna estación policial o, simplemente, a las tres de la madrugada recibía una delegación mexicana para jugar una partida después de conversar sobre los temas generales comunes. Ernesto Guevara, eternamente Che, revolucionario integral y multifacético, sintió gran afición por los deportes y aunque por lo general se le cita como amante del ajedrez y el fútbol, también, desde niño, practicó con derroche de coraje y voluntad otros no tan divulgados. A sus prácticas deportivas también se entregó con la voluntad, coraje y pasión que lo caracterizaron a lo largo de su vida. Luego del triunfo de la Revolución cubana, en la que ganó  los grados de Comandante, hubo  un deporte priorizado  en la vida del Che: el Ajedrez.  Dos veces ganó en los campeonatos patrocinados por el Ministerio de Industria, que él presidía,  y participó, además, en los Torneos del INDER donde ascendió, por los resultados alcanzados, a la primera categoría. Se enfrentó en partidas simultáneas a varios de los mejores jugadores de esos días, entre ellos los grandes maestros soviéticos Victor Korchnoi y Mijail Tal y el argentino Miguel Najdorf, d

Il museo che non c’è. Note sulla dispersione del patrimonio in Gran Bretagna

Directory of Open Access Journals (Sweden)

Caroline Patey

2011-03-01

Full Text Available Indifferente alla loro recente moltiplicazione come al sodalizio che vi si celebra con l’architettura di grido, un fantasma si aggira per i musei. Sordo al nome di Jean Nouvel (Reina Sofia, Louvre quanto a quelli di Herzog & De Meuron (Tate Modern, impermeabile ai fasti del British Museum (Norman Foster come ai restauri della Tate Britain (James Stirling, disinteressato alle fortune del ‘nuovo’ Victoria and Albert Museum e malinconico come si addice alla sua natura, il fantasma invita a interrogare tanta luccicante spettacolarità e forse a non dimenticare che, per quanto custode di memoria e guardiano di culture, il museo è anche il luogo dove vengono consumate, direttamente o meno, amnesie e damnatio memoriae e in nome del quale continuano a perpetrarsi non poche violazioni e disseminazioni.

Inhibition pathways of the potent organophosphate CBDP with cholinesterases revealed by X-ray crystallographic snapshots and mass spectrometry

International Nuclear Information System (INIS)

Carletti, Eugenie; Santoni, Gianluca; Colletier, Jacques-Philippe; Schopfer, Lawrence M.; Lockridge, Oksana; Masson, Patrick; Nachon, Florian; Weik, Martin

2013-01-01

Tri-o-cresyl-phosphate (TOCP) is a common additive in jet engine lubricants and hydraulic fluids suspected to have a role in aero-toxic syndrome in humans. TOCP is metabolized to cresyl saligenin phosphate (CBDP), a potent irreversible inhibitor of butyrylcholinesterase (BChE), a natural bio-scavenger present in the bloodstream, and acetylcholinesterase (AChE), the off-switch at cholinergic synapses. Mechanistic details of cholinesterase (ChE) inhibition have, however, remained elusive. Also, the inhibition of AChE by CBDP is unexpected, from a structural standpoint, i.e., considering the narrowness of AChE active site and the bulkiness of CBDP. In the following, we report on kinetic X-ray crystallography experiments that provided 2.7-3.3 Angstroms snapshots of the reaction of CBDP with mouse AChE and human BChE. The series of crystallographic snapshots reveals that AChE and BChE react with the opposite enantiomers and that an induced-fit rearrangement of Phe297 enlarges the active site of AChE upon CBDP binding. Mass spectrometry analysis of aging in either H 2 16 O or H 2 18 O furthermore allowed us to identify the inhibition steps, in which water molecules are involved, thus providing insights into the mechanistic details of inhibition. X-ray crystallography and mass spectrometry show the formation of an aged end product formed in both AChE and BChE that cannot be reactivated by current oxime-based therapeutics. Our study thus shows that only prophylactic and symptomatic treatments are viable to counter the inhibition of AChE and BChE by CBDP. (authors)

The Anticholinergic and Antiglutamatergic Drug Caramiphen Reduces Seizure Duration in Soman-Exposed Rats: Synergism with the Benzodiazepine Diazepam

Science.gov (United States)

2012-01-01

progress to self-sustained seizures ( status epilepticus , SE) and result in extensive neuropathology as seen in rats (de Araujo Furtado et al., 2009, 2010...physostigmineOP organophosphorus BuChE butyrylcholinesterase ChE cholinesterase SE status epilepticus ATR atropine sulfate 2-PAM 2-pralidoxime NMDA N...L.C., Lichtenstein, S., Yourick, D.L., 2010. Spontaneous recurrent seizures after status epilepticus induced by soman in Sprague-Dawley rats

The chemotaxis-like Che1 pathway has an indirect role in adhesive cell properties of Azospirillum brasilense.

Science.gov (United States)

Siuti, Piro; Green, Calvin; Edwards, Amanda Nicole; Doktycz, Mitchel J; Alexandre, Gladys

2011-10-01

The Azospirillum brasilense chemotaxis-like Che1 signal transduction pathway was recently shown to modulate changes in adhesive cell surface properties that, in turn, affect cell-to-cell aggregation and flocculation behaviors rather than flagellar-mediated chemotaxis. Attachment to surfaces and root colonization may be functions related to flocculation. Here, the conditions under which A. brasilense wild-type Sp7 and che1 mutant strains attach to abiotic and biotic surfaces were examined using in vitro attachment and biofilm assays combined with atomic force microscopy and confocal microscopy. The nitrogen source available for growth is found to be a major modulator of surface attachment by A. brasilense and could be promoted in vitro by lectins, suggesting that it depends on interaction with surface-exposed residues within the extracellular matrix of cells. However, Che1-dependent signaling is shown to contribute indirectly to surface attachment, indicating that distinct mechanisms are likely underlying flocculation and attachment to surfaces in A. brasilense. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Adverse Effects of Cholinesterase Inhibitors in Dementia, According to the Pharmacovigilance Databases of the United-States and Canada.

Directory of Open Access Journals (Sweden)

Thibault B Ali

Full Text Available This survey analyzes two national pharmacovigilance databases in order to determine the major adverse reactions observed with the use of cholinesterase inhibitors in dementia. We conducted a statistical analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS and the Canada Vigilance Adverse Reaction Database (CVARD concerning the side effects of cholinesterase inhibitors. The statistics calculated for each adverse event were the frequency and the reporting odds ratios (ROR. A total of 9877 and 2247 reports were extracted from the FAERS and CVARD databases, respectively. A disproportionately higher frequency of reports of death as an adverse event for rivastigmine, compared to the other acetylcholinesterase inhibiting drugs, was observed in both the FAERS (ROR = 3.42; CI95% = 2.94-3.98; P<0.0001 and CVARD (ROR = 3.67; CI95% = 1.92-7.00; P = 0.001 databases. While cholinesterase inhibitors remain to be an important therapeutic tool against Alzheimer's disease, the disproportionate prevalence of fatal outcomes with rivastigmine compared with alternatives should be taken into consideration.

Reading Strategies: Issues in the Computerization of Machiavelli's "Il demonio che prese moglie".

Science.gov (United States)

Morgan, Leslie Zarker

1994-01-01

The ideal computer-based foreign language reading program must include cognitive background, a learning taxonomy, sound computer design, and knowledge of what is needed for the specific language. Machiavelli's "Il demonia che prese moglie" is chosen for study due to its historical interest. (63 references) (CK)

Activities of cholinesterase enzyme among diazinon and sevin insecticides sprayers in the western part of Iran

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Ali Jalilian

2016-10-01

Full Text Available Objective: To measure the activities of cholinesterase enzyme among farmers who used the selected insecticides for the purpose of preventing the growth of agricultural pests on their farms. Methods: A total of 21 people used diazinon to spray their agricultural lands and 13 people also used sevin to spray theirs in western part of Iran. Lovi Bond method was used for the measurement of cholinesterase activity. Results: Results revealed that the enzyme level before spraying with diazinon was 100.0% among 3 workers and 87.5% in 18 of them. This level decreased to 75.0% among 13 workers and 67.5% in 5 workers. The number of workers that had headache, pale, dizziness with headache, nausea, diarrhea with cramps and stomachache were 5, 9, 5, 3, 4 and 7 respectively. These symptoms decreased after 72 h. Out of 13 workers who sprayed with sevin, the enzyme level before spraying was normal (100.0% among 5 workers and 87.5% in 8 workers. After spraying, the enzyme level was 87.5% in 5 workers, 75.0% in 5 workers and 67.5% in 3 workers. Conclusions: These workers were in danger of chemical poisoning. Measurement of precholinesterase and post-cholinesterase exposures is recommended in order to compare the values after pesticide application.

Open Day at Crèche and School of the CERN Staff Association

CERN Multimedia

Staff Association

2018-01-01

In the morning of Saturday, 3 March 2018, the Crèche and School of the CERN Staff Association opened its doors for parents who wished to visit the establishment. Once again, the Open Day was a great success and brought together more than 50 families for two information sessions, which included: a general presentation of the establishment by the Headmistress, and a visit of the facilities led by the Headmistress and her deputy. At the end of the visit, parents were invited for a drink. This was an opportunity for both parents and professionals to have interesting discussions regarding the general conditions of the establishment and the pedagogical approach applied in the crèche and the school. The management team was delighted to offer the parents the opportunity to participate in this event, where everyone could express their views, ask questions and find answers in a friendly and relaxed atmosphere.

Astrobiological Significance of Definitive Mineralogical Analysis of Martian Surface Samples Using the CheMin XRD/XRF Instrument

Science.gov (United States)

Feldman, S. M.; Blake, D. F.; Sarrazin, P.; Bish, D. L.; Chipera, S. J.; Vaniman, D. T.; Collins, S.

2004-01-01

The search for evidence of habitability, or of extant or extinct life on Mars, will initially be a search for evidence of past or present conditions supportive of life. The three key requirements for the emergence of life are thought to be liquid water; a suitable energy source; and chemical building blocks. CheMin is a miniaturized XRD/XRF (X-Ray diffraction / X-ray fluorescence) instrument which has been developed for definitive mineralogic analysis of soils and rocks on the Martian surface. The CheMin instrument can provide information that is highly relevant to each of these habitability requirements as summarized below.

Trent'anni che sconvolsero la fisica la storia della teoria dei quanti

CERN Document Server

Gamow, George

1993-01-01

Gli anni dal 1900 al 1930 hanno portato un profondo mutamento nella visione che l'uomo aveva dell'universo: tra la prima idea di Max Planck dei quanti di luce nel 1900, e la previsione dell'esistenza delle antiparticelle formulata da P. A. M. Dirac nel 1929, corre un periodo di emozionanti progressi nel campo della fisica teorica.

La chiesa che si fa presepe: visita al Presepe della Chiesa del Rosario di Mottola

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Susy Bigontina

2012-01-01

Full Text Available Abstract – IT In occasione del Natale, la vie della città di Mottola (Ta, Italia fioriscono di presepi, che i visitatori possono liberamente ammirare. Quella del presepe è una tradizione molto sentita dagli abitanti della cittadina pugliese, nella quale viene allestito un grande presepe che occupa e cela l’intera navata della Chiesa del Ss. Sacramento e Rosario. Gli allestitori, appartenenti ad una storica Confraternita locale dedicano settimane a costruire un presepe plastico della Betlemme nella notte di Natale, che mescola icone della tradizione italiana della Natività – alcuni pezzi, ad esempio, sono preziosi manufatti di scuola napoletana – ed elementi naturali tipici della terra delle gravine. Il presepe del Rosario, inoltre, mostra un’interessante ricerca dell’effetto prospettico e forse un ancor più interessante cornice di ciclicità, ottenuta tramite l’alternanza del giorno e della notte, musica ed effetti sonori, che proietta la scena verso un orizzonte atemporale. Questo articolo nasce dalla visita degli autori a Mottola, in occasione della presentazione del libro La Settimana Santa a Mottola, di cui essi sono stati co-autori, e quindi rappresenta il frutto di un nuovo capitolo di lavoro con la viva comunità mottolese ed i suoi riti. Abstract – FR Pour l'occasion de Noël, les rues de la villes de Mottola (Ta, Italie sont embellies de crèches que les visiteurs peuvent admirer en toute liberté. La tradition de la crèche est une tradition très ressentie par les habitants de la petite ville pugliaise, dans laquelle on prépare une grande crèche qui occupe et cache tout le nef de l'église du très Ss. Sacramento e Rosario. Les préparateurs qui appartiennent à une Confrérie historique locale dédient plusieurs semaines pour la construction d'une crèche comme celle de Betleemme de la nuit de Noël - certaines pièces, par exemple, sont de précieux produits manufacturés provenant de l'école napolitaine - et

(-)-Meptazinol-melatonin hybrids as novel dual inhibitors of cholinesterases and amyloid-β aggregation with high antioxidant potency for Alzheimer's therapy.

Science.gov (United States)

Cheng, Shaobing; Zheng, Wei; Gong, Ping; Zhou, Qiang; Xie, Qiong; Yu, Lining; Zhang, Peiyi; Chen, Liangkang; Li, Juan; Chen, Jianxing; Chen, Hailin; Chen, Hongzhuan

2015-07-01

The multifactorial pathogenesis of Alzheimer's disease (AD) implicates that multi-target-directed ligands (MTDLs) intervention may represent a promising therapy for AD. Amyloid-β (Aβ) aggregation and oxidative stress, two prominent neuropathological hallmarks in patients, play crucial roles in the neurotoxic cascade of this disease. In the present study, a series of novel (-)-meptazinol-melatonin hybrids were designed, synthesized and biologically characterized as potential MTDLs against AD. Among them, hybrids 7-7c displayed higher dual inhibitory potency toward cholinesterases (ChEs) and better oxygen radical absorbance capacity (ORAC) than the parental drugs. Furthermore, compound 7c could effectively inhibit Aβ self-aggregation, showed favorable safety and the blood-brain barrier (BBB) permeability. Therefore, 7c may serve as a valuable candidate that is worthy of further investigations in the treatment of AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Correlation and interconversion between erythrocyte cholinesterase values obtained by the Michel and the EQM techniques].

Science.gov (United States)

Carmona-Fonseca, Jaime

2006-12-01

Several techniques are available to measure red cell cholinesterase; therefore, evaluations with several methods provide a measure of concordance. An equation was formulated to transform native data of reference values to reference units of cholinesterase activity as measured by Michel and EQM tests. The experimental design was descriptive, transversal and prospective. The group sampled was a representative adult working population, aged 18-75, without previous exposure to cholinesterase inhibitors pesticides. The individuals were affiliated to the Social Security System and resided in Valle de Aburrá and Cercano Oriente Antioqueño (Antioquia Province, northwestern Colombia). Of 827 individuals, quantitative erythrocytes (Michel y EQM) tests exhibited "r" coefficients between 0.67 and R2 coefficient of 44%.,This indicated that one test explained the results in other test in 44% of the cases. The corelation was higher in Aburrá than in Oriente. The linear model for the 827 individuals was as follows: EQM U/g oxy-hemoglobin = 9.575 U/ g oxy-hemoglobin + 29.791 (Michel delta pH/hour). Michel delta pH/hr = 0.3312 delta pH/hour + 0.0149 (EQM U/g oxy-hemoglobin), where EQM was expressed in U/g oxy-hemoglobin and Michel pH change/hr. Inter-sections (coefficient a) and inclines (coefficient b) were significant in this model. In the adjusted equations, after exclusion of 12 extreme data (1.5% of 827), the r coefficient increased from 0.67 to 0.72 The adjusted equations were as follows: EQM U/g oxy-hemoglobin = 8.1884 U/g oxy-hemoglobin + 31.3920 (Michel delta pH/hour); Michel delta pH/hr = 0.2925 delta pH/hr + 0.0161 (EQM U/g oxy-hemoglobin). This system of linear equations permitted the transformation of Michel (delta PH/ hr) units to EQM (U/g oxy-hemoglobin) units and vice versa. This will facilitate data comparisons by clinicians and epidemiologists who are using these methods of cholinesterase measurement.

Association between blood cholinesterase activity, organophosphate pesticide residues on hands, and health effects among chili farmers in Ubon Ratchathani Province, northeastern Thailand

Science.gov (United States)

Nganchamung, Thitirat; Robson, Mark G; Siriwong, Wattasit

Use of pesticides has been documented to lead to several adverse health effects. Farmers are likely to be exposed to pesticides through dermal exposure as a result of mixing, loading, and spraying. Organophosphate pesticides (OPs) are widely used in most of the agricultural areas throughout Thailand. OPs are cholinesterase inhibitors and blood cholinesterase activity is used as a biomarker of OP effects. This study aims to determine the association between blood cholinesterase activity and organophosphate pesticide residues on chili farmer’s hands and their adverse health effects. Ninety chili farmers directly involved with pesticide applications (e.g. mixing, loading, spraying) were recruited and were interviewed face to face. Both enzymes, erythrocyte acetylcholinesterase (AChE) and plasma cholinesterase (PChE), were tested with the EQM Test-mate Cholinesterase Test System (Model 400). Hand wipe samples were used for collecting residues on both hands and OP residues for chlorpyrifos and profenofos were quantified using gas chromatography equipped with a flame photometric detector (GC-FPD). The average activity (±SD) of AChE and PChE was 2.73 (±0.88) and 1.58 (±0.56) U/mL, respectively. About 80.0% of the participants had detectable OP residues on hands. The median residues of chlorpyrifos and profenofos were found to be 0.02 and 0.03 mg/kg/two hands, respectively. Half of participants reported having some acute health symptoms within 48 hours after applying pesticides. When adjusted for gender, number of years working in chili farming, and frequency of pesticide use, AChE activity (Adjusted OR = 0.03, 95%CI: 0.01-0.13) and detected OP residues on hands (Adjusted OR = 0.15, 95%CI: 0.02-0.95) were significantly associated with having health effects, but no significant association was found in PChE activity (Adjusted OR = 2.09, 95%CI: 0.63-6.99). This study suggests that regular monitoring for blood cholinesterase and effective interventions to reduce pesticide

The influence of cholinesterase inhibitor therapy for dementia on risk of cardiac pacemaker insertion: a retrospective, population-based, health administrative databases study in Ontario, Canada.

Science.gov (United States)

Huang, Allen R; Redpath, Calum J; van Walraven, Carl

2015-04-28

Cholinesterase inhibitors are used to treat the symptoms of dementia and can theoretically cause bradycardia. Previous studies suggest that patients taking these medications have an increased risk of undergoing pacemaker insertion. Since these drugs have a marginal impact on patient outcomes, it might be preferable to change drug treatment rather than implant a pacemaker. This population-based study determined the association of people with dementia exposed to cholinesterase inhibitor medication and pacemaker insertion. We used data from the Ontario health administrative databases from January 1, 1993 to June 30, 2012. We included all community-dwelling seniors who had a code for dementia and were exposed to cholinesterase inhibitors (donezepil, galantamine, and rivastigmine) and/or drugs used to treat co-morbidities of hypertension, diabetes, depression and hypothyroidism. We controlled for exposure to anti-arrhythmic drugs. Observation started at first exposure to any medication and continued until the earliest of pacemaker insertion, death, or end of study. 2,353,909 people were included with 96,000 (4.1%) undergoing pacemaker insertion during the observation period. Case-control analysis showed that pacemaker patients were less likely to be coded with dementia (unadjusted OR 0.42 [95%CI 0.41-0.42]) or exposed to cholinesterase inhibitors (unadjusted OR 0.39 [95%CI 0.37-0.41]). That Cohort analysis showed patients with dementia taking cholinesterase inhibitors had a decreased risk of pacemaker insertion (unadj-HR 0.58 [0.55-0.61]). Adjustment for patient age, sex, and other medications did not notably change results, as did restricting the analysis to incident users. Patients taking cholinesterase inhibitors rarely undergo, and have a significantly reduced risk of, cardiac pacemaker insertion.

Pre-therapeutic factors for predicting survival after radioembolization: a single-center experience in 389 patients

International Nuclear Information System (INIS)

Paprottka, K.J.; Schoeppe, F.; Ingrisch, M.; Ruebenthaler, J.; Sommer, N.N.; Paprottka, P.M.; Toni, E. de; Ilhan, H.; Zacherl, M.; Todica, A.

2017-01-01

To determine pre-therapeutic predictive factors for overall survival (OS) after yttrium (Y)-90 radioembolization (RE). We retrospectively analyzed the pre-therapeutic characteristics (sex, age, tumor entity, hepatic tumor burden, extrahepatic disease [EHD] and liver function [with focus on bilirubin and cholinesterase level]) of 389 consecutive patients with various refractory liver-dominant tumors (hepatocellular carcinoma [HCC], cholangiocarcinoma [CCC], neuroendocrine tumor [NET], colorectal cancer [CRC] and metastatic breast cancer [MBC]), who received Y-90 radioembolization for predicting survival. Predictive factors were selected by univariate Cox regression analysis and subsequently tested by multivariate analysis for predicting patient survival. The median OS was 356 days (95% CI 285-427 days). Stable disease was observed in 132 patients, an objective response in 71 (one of which was complete remission) and progressive disease in 122. The best survival rate was observed in patients with NET, and the worst in patients with MBC. In the univariate analyses, extrahepatic disease (P < 0.001), large tumor burden (P = 0.001), high bilirubin levels (>1.9 mg/dL, P < 0.001) and low cholinesterase levels (CHE <4.62 U/I, P < 0.001) at baseline were significantly associated with poor survival. Tumor entity, tumor burden, extrahepatic disease and CHE were confirmed in the multivariate analysis as independent predictors of survival. Sex, applied RE dose and age had no significant influence on OS. Pre-therapeutic baseline bilirubin and CHE levels, extrahepatic disease and hepatic tumor burden are associated with patient survival after RE. Such parameters may be used to improve patient selection for RE of primary or metastatic liver tumors. (orig.)

Pre-therapeutic factors for predicting survival after radioembolization: a single-center experience in 389 patients

Energy Technology Data Exchange (ETDEWEB)

Paprottka, K.J.; Schoeppe, F.; Ingrisch, M.; Ruebenthaler, J.; Sommer, N.N.; Paprottka, P.M. [LMU - University of Munich, Department of Clinical Radiology, Munich (Germany); Toni, E. de [LMU - University of Munich, Department of Hepatology, Munich (Germany); Ilhan, H.; Zacherl, M.; Todica, A. [LMU - University of Munich, Department of Nuclear Medicine, Munich (Germany)

2017-07-15

To determine pre-therapeutic predictive factors for overall survival (OS) after yttrium (Y)-90 radioembolization (RE). We retrospectively analyzed the pre-therapeutic characteristics (sex, age, tumor entity, hepatic tumor burden, extrahepatic disease [EHD] and liver function [with focus on bilirubin and cholinesterase level]) of 389 consecutive patients with various refractory liver-dominant tumors (hepatocellular carcinoma [HCC], cholangiocarcinoma [CCC], neuroendocrine tumor [NET], colorectal cancer [CRC] and metastatic breast cancer [MBC]), who received Y-90 radioembolization for predicting survival. Predictive factors were selected by univariate Cox regression analysis and subsequently tested by multivariate analysis for predicting patient survival. The median OS was 356 days (95% CI 285-427 days). Stable disease was observed in 132 patients, an objective response in 71 (one of which was complete remission) and progressive disease in 122. The best survival rate was observed in patients with NET, and the worst in patients with MBC. In the univariate analyses, extrahepatic disease (P < 0.001), large tumor burden (P = 0.001), high bilirubin levels (>1.9 mg/dL, P < 0.001) and low cholinesterase levels (CHE <4.62 U/I, P < 0.001) at baseline were significantly associated with poor survival. Tumor entity, tumor burden, extrahepatic disease and CHE were confirmed in the multivariate analysis as independent predictors of survival. Sex, applied RE dose and age had no significant influence on OS. Pre-therapeutic baseline bilirubin and CHE levels, extrahepatic disease and hepatic tumor burden are associated with patient survival after RE. Such parameters may be used to improve patient selection for RE of primary or metastatic liver tumors. (orig.)

Synthesis, crystal structure determination, biological screening and docking studies of N1-substituted derivatives of 2,3-dihydroquinazolin-4(1H)-one as inhibitors of cholinesterases.

Science.gov (United States)

Sultana, Nargis; Sarfraz, Muhammad; Tanoli, Saba Tahir; Akram, Muhammad Safwan; Sadiq, Abdul; Rashid, Umer; Tariq, Muhammad Ilyas

2017-06-01

Pursuing the strategy of developing potent AChE inhibitors, we attempted to carry out the N 1 -substitution of 2,3-dihydroquinazolin-4(1H)-one core. A set of 32 N-alkylated/benzylated quinazoline derivatives were synthesized, characterized and evaluated for their inhibition against cholinesterases. N-alkylation of the series of the compounds reported previously (N-unsubstituted) resulted in improved activity. All the compounds showed inhibition of both enzymes in the micromolar to submicromolar range. Structure activity relationship (SAR) of the 32 derivatives showed that N-benzylated compounds possess good activity than N-alkylated compounds. N-benzylated compounds 2ad and 2af were found very active with their IC 50 values toward AChE in submicromolar range (0.8µM and 0.6µM respectively). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. Computational predictions of ADMET studies reveal that all the compounds have good pharmacokinetic properties with no AMES toxicity and carcinogenicity. Moreover, all the compounds are predicted to be absorbed in human intestine and also have the ability to cross blood brain barrier. Overall, the synthesized compounds have established a structural foundation for the design of new inhibitors of cholinesterase. Copyright © 2017 Elsevier Inc. All rights reserved.

Caregiver Acceptance of Adverse Effects and Use of Cholinesterase Inhibitors in Alzheimer's Disease

Science.gov (United States)

Oremus, Mark; Wolfson, Christina; Vandal, Alain C.; Bergman, Howard; Xie, Qihao

2007-01-01

Caregivers play a determining role in choosing treatments for persons with Alzheimer's disease. The objective of this study was to examine caregivers' willingness to have persons with Alzheimer's disease continue taking cholinesterase inhibitors in the event that any 1 of 11 adverse effects was to occur. Data were gathered via postal questionnaire…

Data from the Mars Science Laboratory CheMin XRD/XRF Instrument

Science.gov (United States)

Vaniman, David; Blake, David; Bristow, Tom; DesMarais, David; Achilles, Cherie; Anderson, Robert; Crips, Joy; Morookian, John Michael; Spanovich, Nicole; Vasavada, Ashwin;

Novel multi-target-directed ligands for Alzheimer's disease: Combining cholinesterase inhibitors and 5-HT6 receptor antagonists. Design, synthesis and biological evaluation.

Science.gov (United States)

Więckowska, Anna; Kołaczkowski, Marcin; Bucki, Adam; Godyń, Justyna; Marcinkowska, Monika; Więckowski, Krzysztof; Zaręba, Paula; Siwek, Agata; Kazek, Grzegorz; Głuch-Lutwin, Monika; Mierzejewski, Paweł; Bienkowski, Przemysław; Sienkiewicz-Jarosz, Halina; Knez, Damijan; Wichur, Tomasz; Gobec, Stanislav; Malawska, Barbara

2016-11-29

As currently postulated, a complex treatment may be key to an effective therapy for Alzheimer's disease (AD). Recent clinical trials in patients with moderate AD have shown a superior effect of the combination therapy of donepezil (a selective acetylcholinesterase inhibitor) with idalopirdine (a 5-HT 6 receptor antagonist) over monotherapy with donepezil. Here, we present the first report on the design, synthesis and biological evaluation of a novel class of multifunctional ligands that combines a 5-HT 6 receptor antagonist with a cholinesterase inhibitor. Novel multi-target-directed ligands (MTDLs) were designed by combining pharmacophores directed against the 5-HT 6 receptor (1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-indole) and cholinesterases (tacrine or N-benzylpiperidine analogues). In vitro evaluation led to the identification of tacrine derivative 12 with well-balanced potencies against the 5-HT 6 receptor (K b  = 27 nM), acetylcholinesterase and butyrylcholinesterase (IC 50 hAChE  = 12 nM, IC 50 hBuChE  = 29 nM). The compound also showed good in vitro blood-brain-barrier permeability (PAMPA-BBB assay), which was confirmed in vivo (open field study). Central cholinomimetic activity was confirmed in vivo in rats using a scopolamine-induced hyperlocomotion model. A novel class of multifunctional ligands with compound 12 as the best derivative in a series represents an excellent starting point for the further development of an effective treatment for AD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Characterization of cholinesterases in Chironomus riparius and the effects of three herbicides on chlorpyrifos toxicity.

Science.gov (United States)

Pérez, Joanne; Monteiro, Marta S; Quintaneiro, Carla; Soares, Amadeu M V M; Loureiro, Susana

2013-11-15

In this study, the toxicities of four pesticides (the herbicides atrazine, terbuthylazine, metolachlor and the insecticide chlorpyrifos) previously detected in the Alqueva reservoir/dam (south of Portugal) were evaluated individually and in binary combinations of the herbicides and the insecticide using fourth-instar larvae of the aquatic midge Chironomus riparius. Chlorpyrifos induced toxicity to midges in all the 48 h toxicity bioassays performed. The swimming behaviour of the larvae was impaired, with EC50 values ranging from 0.15 to 0.17 μg/L. However, neither s-triazine (atrazine and terbuthylazine) herbicides nor metolachlor alone at concentrations up to 200 μg/L caused significant toxicity to C. riparius. When combined with both s-triazine herbicides, chlorpyrifos toxicity was enhanced by approximately 2-fold when tested in a binary mixture experimental setup, at the 50% effective concentration levels. To evaluate how chlorpyrifos toxicity was being increased, the cholinesterases (ChE) were characterized biochemically using different substrates and selective inhibitors. The results obtained suggested that the main enzyme present in this species is acetylcholinesterase (AChE) and therefore it was assayed upon C. riparius exposures to all pesticides individually and as binary mixtures. Although atrazine and terbuthylazine are not effective inhibitors of AChE, the potentiation of chlorpyrifos toxicity by the two s-triazine herbicides was associated with a potentiation in the inhibition of AChE in midges; both s-triazine herbicides at 200 μg/L increased the inhibition of the AChE activity by 7 and 8-fold, respectively. A strong correlation was observed between swimming behaviour disturbances of larvae and the inhibition of the AChE activity. In contrast, metolachlor did not affect chlorpyrifos toxicity at any of the concentrations tested. Therefore, the herbicides atrazine and terbuthylazine can act as synergists in the presence of chlorpyrifos, increasing

Novel N-allyl/propargyl tetrahydroquinolines: Synthesis via Three-component Cationic Imino Diels-Alder Reaction, Binding Prediction, and Evaluation as Cholinesterase Inhibitors.

Science.gov (United States)

Rodríguez, Yeray A; Gutiérrez, Margarita; Ramírez, David; Alzate-Morales, Jans; Bernal, Cristian C; Güiza, Fausto M; Romero Bohórquez, Arnold R

2016-10-01

New N-allyl/propargyl 4-substituted 1,2,3,4-tetrahydroquinolines derivatives were efficiently synthesized using acid-catalyzed three components cationic imino Diels-Alder reaction (70-95%). All compounds were tested in vitro as dual acetylcholinesterase and butyryl-cholinesterase inhibitors and their potential binding modes, and affinity, were predicted by molecular docking and binding free energy calculations (∆G) respectively. The compound 4af (IC50 = 72 μm) presented the most effective inhibition against acetylcholinesterase despite its poor selectivity (SI = 2), while the best inhibitory activity on butyryl-cholinesterase was exhibited by compound 4ae (IC50 = 25.58 μm) with considerable selectivity (SI = 0.15). Molecular docking studies indicated that the most active compounds fit in the reported acetylcholinesterase and butyryl-cholinesterase active sites. Moreover, our computational data indicated a high correlation between the calculated ∆G and the experimental activity values in both targets. © 2016 The Authors Chemical Biology & Drug Design Published by John Wiley & Sons Ltd.

Terpenes, Phenylpropanoids, Sulfur and Other Essential Oil Constituents as Inhibitors of Cholinesterases.

Science.gov (United States)

Burcul, Franko; Blazevic, Ivica; Radan, Mila; Politeo, Olivera

2018-03-29

Essential oils constituents are a diverse family of low molecular weight organic compounds with comprehensive biological activity. According to their chemical structure these active compounds can be divided into four major groups: terpenes, terpenoids, phenylpropenes, and "others". In addition, they may contain diverse functional groups according to which they can be classified as hydrocarbons (monoterpenes, sesquiterpenes, and aliphatic hydrocarbons); oxygenated compounds (monoterpene and sesquiterpene alcohols, aldehydes, ketones, esters, and other oxygenated compounds); and sulfur and/or nitrogen sulfur-containing compounds (thioesters, sulfides, isothiocyantes, nitriles, and others). Compounds that act as cholinesterase inhibitors still represent the only pharmacological treatment of Alzheimer´s disease. Numerous in vitro studies showed that some compounds, found in essential oils, have a promising cholinesterase inhibitory activity, such as α-pinene, δ-3-carene, 1,8-cineole, carvacrol, thymohydroquinone, α- and β-asarone, anethole, etc. This review summarizes the most relevant research published to date on essential oil constituents and their acetylcholinesterase/butyrylcholinesterase inhibitory potential as well as their structure related activity, synergistic and antagonistic effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

European analytical column No. 36 from the Division of Analytical Chemistry (DAC) of the European Association for Chemical and Molecular Sciences (EuCheMS)

DEFF Research Database (Denmark)

Karlberg, Bo; Emons, Hendrik; Andersen, Jens Enevold Thaulov

2008-01-01

European analytical column no. 36 from the division of analytical chemistry (DAC) of the European association for chemical and molecular sciences (EuCheMS)......European analytical column no. 36 from the division of analytical chemistry (DAC) of the European association for chemical and molecular sciences (EuCheMS)...

Effects of Agricultural Management Policies on the Exposure of Black-Winged Stilts (Himantopus himantopus Chicks to Cholinesterase-Inhibiting Pesticides in Rice Fields.

Directory of Open Access Journals (Sweden)

Gregorio M Toral

Full Text Available Levels of exposure to pesticides in rice fields can be significant depending on the environmental policies practiced. The aim of European Union integrated management policy is to reduce pesticide use and impact on environment. Rice fields provide an alternative breeding habitat for many waterbirds that are exposed to the pesticides used and therefore can be valuable indicators of their risk for wildlife. To evaluate integrated management success we examined exposure of Black-winged Stilts (Himantopus himantopus to cholinesterase-inhibiting pesticides in rice fields under different types of management by measuring plasma cholinesterase activity. Cholinesterase activity was lower in birds sampled in (a 2008 after a period of intense pesticide application, than in (b 2005-2007 and 2011 in rice fields subject to integrated management in Doñana (SW Spain and (c in control natural wetlands in Spain and Morocco. During 2009 and 2010, cholinesterase activity was lower in rice fields in Doñana than in rice fields in Larache and Sidi Allal Tazi (NW Morocco. Our results suggest that integrated management successfully reduced the exposure of Black-winged Stilts to pesticides in most of the years. Care should be taken to implement mosquito and pest crop controls on time and with environmentally friendly products in order to reduce its impact on wildlife.

Il mito della precarietà: quando la precarietà è un valore che decostruisce l’immaginario della precarietà

Directory of Open Access Journals (Sweden)

Antonio Casillo

2011-07-01

Full Text Available Oggi la ricerca del posto “fisso” sembra essere il sogno irraggiungibile di molti giovani precari e la “flessibilità”, una parola d’ordine con cui si aspirava a riformare il mondo del lavoro e che tanto in voga sembrava essere negli anni ’90, è diventata sinonimo di incertezza, precarietà, se non addirittura sfruttamento. Ma c’era chi proprio nel lavoro che oggi definiremo precario, vedeva l’unica possibilità per restare libero dalle leggi di mercato e dai potenti poteri editoriali Newyorkesi. In questo articolo proviamo a gettare uno sguardo al mito letterario con cui, il rifiutare un posto fisso, significava rivendicare la propria libertà, un mito romantico certo, e sicuramente distante dalla realtà, ma che ha affascinato un’intera generazione di scrittori, poeti, musicisti. Da Jack London, passando attraverso la San Francisco Renaissance e la Beat Generation, fino ad arrivare al fenomeno della così detta generazione Hippy, il sogno americano sembrava essere quello di una frontiera mobile in cui, la strada, sembrava non avere mai fine.

Effects of dietary ABATE® on reproductive success, duckling survival, behavior, and clinical pathology in game-farm mallards

Science.gov (United States)

Franson, J. Christian; Spann, James W.; Heinz, Gary; Bunck, Christine M.; Lamont, Thair

1983-01-01

Forty-four pairs of game-farm mallards (Anas platyrhynchos) were fed ABATE® 4E (temephos) to yield 0, 1, or 10 ppm ABATE® beginning before the initiation of lay, and terminating when ducklings were 21 days of age. The mean interval between eggs laid was greater for hens fed 10 ppm ABATE® than for controls. Clutch size, fertility, hatchability, nest attentiveness of incubating hens, and avoidance behavior of ducklings were not significantly affected by ABATE® ingestion. The percentage survival of ducklings to 21 days of age was significantly lower in both treated groups than in controls, but brain acetylcholinesterase (AChE) activity was not inhibited in young which died before termination of the study. In 21-day-old ducklings, aspartate aminotransferase (AST) activity increased and plasma nonspecific cholinesterase (ChE) activity was inhibited by about 20% in both treatment groups, but there were no significant differences in brain AChE or plasma alanine aminotransferase (ALT) activities, or plasma uric acid concentration. Clinical chemistry values of adults were not affected. No ABATE®, ABATE® sulfoxide, or ABATE® sulfone residues were found in eggs or tissue samples.

A technician monitors the CHeX, a USMP-4 experiment which will be flown on STS-87, in the SSPF

Science.gov (United States)

1997-01-01

United States Microgravity Payload-4 (USMP-4) experiments are prepared to be flown on Space Shuttle mission STS-87 in the Space Station Processing Facility at Kennedy Space Center (KSC). Here, a technician is monitoring the Confined Helium Experiment, or CHeX, that will use microgravity to study one of the basic influences on the behavior and properties of materials by using liquid helium confined between silicon disks. CHeX and several other experiments are scheduled for launch aboard STS-87 on Nov. 19 from KSC.

The intracellular domain of the Drosophila cholinesterase-like neural adhesion protein, gliotactin, is natively unfolded

NARCIS (Netherlands)

Zeev-Ben-Mordehai, T; Rydberg, EH; Solomon, A.; Toker, L; Auld, VJ; Silman, I.; Botti, S; Sussman, J.L.

2003-01-01

Drosophila gliotactin (Gli) is a 109-kDa transmembrane, cholinesterase-like adhesion molecule (CLAM), expressed in peripheral glia, that is crucial for formation of the blood-nerve barrier. The intracellular portion (Gli-cyt) was cloned and expressed in the cytosolic fraction of Escherichia coli

Pretreatment with P-Nitrophenyl Phosphoramides: Spontaneous Reactivation of Blood ChE after Oral Administration to Guinea Pigs

National Research Council Canada - National Science Library

Polhuijs, M

1997-01-01

... and of the reference compounds pyridostigmine and physostigmine has been studied in the guinea pig, as determined by measuring spontaneous reactivation of blood ChE inhibited by these pretreatment compounds...

Species-specific patterns of swimming escape performance and cholinesterase activity in a guild of aquatic insects exposed to endosulfan

International Nuclear Information System (INIS)

Trekels, Hendrik; Van de Meutter, Frank; Stoks, Robby

2012-01-01

Next to imposing direct lethal effects, pollutants may also indirectly impose mortality by making prey organisms more vulnerable to predation. We report that four water boatmen species differed strongly in direct endosulfan-imposed mortality, and only the species that suffered highest mortality, Sigara iactans, also showed a reduction in escape swimming speed. While head AChE activity was inhibited in all four species, body ChE was only inhibited in S. iactans where it covaried with escape swimming speed, indicating a mechanistic link between body ChE and swimming speed. Our study underscores the need for risk assessment to consider sublethal pollutant effects, which may considerably affect survival rates under natural conditions, also when testing concentrations of a pesticide that cause direct mortality. Such sublethal effects may generate discrepancies between laboratory and field studies and should be considered when designing safety factors for toxicants where the risk assessment is solely based on LC50 values. - Highlights: ► Endosulfan, even at lethal levels, did not affect swimming propensity when attacked. ► Endosulfan reduced escape swimming in one out of four tested corixid species. ► Lower body ChE levels were associated with a slower escape speed in one species. ► Head AChE activity was more sensitive to endosulfan than body ChE. ► Endosulfan had strongly different effects on the closely related species. - Endosulfan only detectably reduced escape swimming speed in one of the four studied water boatmen species and this was associated with an inhibition of body ChE.

Studies on the molecular dissection of human cholinesterase variants and their genomic origins. Final report, 1 June 1994-30 May 1996

Energy Technology Data Exchange (ETDEWEB)

Soreq, H.

1996-06-01

To evaluate the capacity of overexpressed recombinant human cholinesterases or mutated variants thereof to confer protection against anti-cholinesterase toxicity, we employed transiently transgenic Xenopus laevis tadpoles and stably transgenic mice. Normal and mutant variants of butyrylcholinesterase (BuChE) revealed partially overlapping binding sites for several inhibitors and demonstrated the involvement of the oxyanion hole in BuChE catalysis. In the developing tadpoles the isoform of AChE, which terminates with the 3`-exon 6, was efficiently accumulated in neuromuscular junctions and conferred resistance to the organophosphate paraoxon. In transgenic mice, exon 6-terminated AChE, under control of its authentic promoter, accumulated in CNS synapses and conferred resistance to paraoxon and several cholinergic agonists, but caused progressive deterioration in both neuromotor and cognitive functioning. Finally, in a human patient carrying the atypical`1 (D7OG) gene for BuChE, we observed adverse responses to prophylactic doses of the carbamate pyridostigmine and from this and in vitro studies predicted a generalized genetic predisposition to anti-cholinesterase therapies, including that approved for the treatment of Alzheimer`s disease.

Neuroprotective effect of seaweeds inhabiting South Indian coastal area (Hare Island, Gulf of Mannar Marine Biosphere Reserve): Cholinesterase inhibitory effect of Hypnea valentiae and Ulva reticulata.

Science.gov (United States)

Suganthy, N; Karutha Pandian, S; Pandima Devi, K

2010-01-14

Alzheimer's disease (AD) is the most common form of dementia, which is one of the four leading causes of death in developed nations. Until date the only symptomatic treatment for this disease is based on the "cholinergic hypothesis" where the drugs enhance acetylcholine levels in the brain by inhibiting acetylcholinesterase (AChE). In the course for screening cholinesterase inhibitors about eight seaweeds, with wide pharmaceutical applications, were collected from Hare Island, Gulf of Mannar, Marine Biosphere Reserve, Tamil Nadu, India. Inhibitory effect of methanol extract of the seaweeds was studied in vitro by incubating various concentration of the extract with AChE or butyryl cholinesterase (BuChE) and assessing their activities by Ellman's colorimetric method. Kinetic parameters like IC(50), K(i) and V(max) were also analyzed. The results showed that of the eight seaweeds screened Hypnea valentiae, Padina gymnospora, Ulva reticulata and Gracilaria edulis exhibited inhibitory activity to AChE with IC(50) value of 2.6, 3.5, 10 and 3mg/ml respectively, while H. valentiae, Enteromorpha intestinalis, Dictyota dichotoma and U. reticulata showed 50% inhibition to BuChE at concentration 3.9, 7, 6.5 and 10mg/ml respectively. The inhibitory activities of the seaweed extracts were comparable to the standard drug donepezil. Enzyme kinetic analysis showed that algal extracts exhibited mixed type inhibition (partial noncompetitive inhibition). Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Report to EuCheMS Division of Analytical Chemistry on CITAC Activity

DEFF Research Database (Denmark)

Andersen, Jens Enevold Thaulov; Wegsheider, Wolfhard

Although the CITAC organisation [1] was founded on traceability, it embraces a variety of concepts allocated specifically to quality assurance. Collaboration with other organisations that promote practices and procedures of quality assurance is essential, and appointed liaison persons...... are encouraged to support this effort. In continuation of this aim a close contact to EuCheMS is desired together with contacts to IUPAC, ISO/REMCO, BIPM/CCQM, ILAC, EA, APLAC, EUROMET, SIM, APMP, AOACI, IAEA, IFCC and SADCMET....

Changes of learning and memory ability and brain nicotinic receptors of rat offspring with coal burning fluorosis

Energy Technology Data Exchange (ETDEWEB)

Gui, C.Z.; Ran, L.Y.; Li, J.P.; Guan, Z.Z. [Guiyang Medical College, Guiyang (China). Dept. of Pathology

2010-09-15

The purpose of the investigation is to reveal the mechanism of the decreased ability of learning and memory induced by coal burning fluorosis. Ten offspring SD rats aged 30 days, who were born from the mothers with chronic coal burning fluorosis, and ten offspring with same age from the normal mothers as controls were selected. Spatial learning and memory of the rats were evaluated by Morris Water Maze test. Cholinesterase activity was detected by photometric method. The expressions of nicotinic acetylcholine receptors (nAChRs) at protein and mRNA levels were detected by Western blotting and Real-time PCR, respectively. The results showed that in the rat offspring exposed to higher fluoride as compared to controls, the learning and memory ability declined; the cholinesterase activities in the brains were inhibited; the protein levels of alpha 3, alpha 4 and alpha 7 nAChR subunits were decreased which showed certain significant correlations with the declined learning and memory ability; and the mRNA levels of alpha 3 and alpha 4 nAChRs were decreased, whereas the alpha 7 mRNA increased. The data indicated that coal burning fluorosis can induce the decreased ability of learning and memory of rat offspring, in which the mechanism might be connected to the changed nAChRs and cholinesterase.

La macchina che cerca Dio. Nasce LHC forse scoprira' Higgs elusiva particella della creazione

CERN Multimedia

Bianucci, P

2003-01-01

"LEON Lederman, premio Nobel per la fisica, l'ha misticamente definita la particella di Dio perche' sarebbe il pilastro sul quale si appoggia tutta la materia dell'universo che conosciamo. Piu' tecnicamente, e' la "particella di Higgs", un bosone previsto dal Modello Standard del microcosmo la cui esistenza sarebbe necessaria per giustificare, anche quantitativamente, la massa di tutte le particelle" (1/2 page).

Initial cognitive response to cholinesterase inhibitors and subsequent long-term course in patients with mild Alzheimer's disease

NARCIS (Netherlands)

Droogsma, Erika; van Asselt, Dieneke; Diekhuis, Marjolein; Veeger, Nic; van der Hooft, Cornelis; De Deyn, Peter Paul

Background: Some guidelines recommend to discontinue treatment with cholinesterase inhibitors (ChEIs) in patients with Alzheimer's disease (AD) without an initial response to ChEI treatment. Evidence supporting this recommendation, however, is limited. This study aimed to investigate the relation

Design, synthesis and evaluation of novel cinnamic acid derivatives bearing N-benzyl pyridinium moiety as multifunctional cholinesterase inhibitors for Alzheimer's disease.

Science.gov (United States)

Lan, Jin-Shuai; Hou, Jian-Wei; Liu, Yun; Ding, Yue; Zhang, Yong; Li, Ling; Zhang, Tong

2017-12-01

A novel family of cinnamic acid derivatives has been developed to be multifunctional cholinesterase inhibitors against AD by fusing N-benzyl pyridinium moiety and different substituted cinnamic acids. In vitro studies showed that most compounds were endowed with a noteworthy ability to inhibit cholinesterase, self-induced Aβ (1-42) aggregation, and to chelate metal ions. Especially, compound 5l showed potent cholinesterase inhibitory activity (IC 50 , 12.1 nM for eeAChE, 8.6 nM for hAChE, 2.6 μM for eqBuChE and 4.4 μM for hBuChE) and the highest selectivity toward AChE over BuChE. It also showed good inhibition of Aβ (1-42) aggregation (64.7% at 20 μM) and good neuroprotection on PC12 cells against amyloid-induced cell toxicity. Finally, compound 5l could penetrate the BBB, as forecasted by the PAMPA-BBB assay and proved in OF1 mice by ex vivo experiments. Overall, compound 5l seems to be a promising lead compound for the treatment of Alzheimer's diseases.

Animals′ Role in Proper Behaviour: Cheŵa Women′s Instructions in South-Central Africa

Directory of Open Access Journals (Sweden)

Leslie F Zubieta

2016-01-01

Full Text Available The most common role of animals in the Cheŵa culture of south-central Africa is twofold: they are regarded as an important source of food, and they also provide raw materials for the creation of traditional medicines. Animals, however, also have a nuanced symbolic role that impacts the way people behave with each other by embodying cultural protocols of proper — and not so proper — behaviour. They appear repeatedly in storytelling and proverbs to reference qualities that people need to avoid or pursue and learn from the moral of the story in which animals interplay with each other, just as humans do. For example, someone who wants to prevent the consequences of greed is often advised to heed hyena stories and proverbs. My contribution elaborates on Brian Morris's instrumental work in south-central Africa, which has permitted us to elucidate the symbolism of certain animals and the perception of landscape for Indigenous populations in this region. I discuss some of the ways in which animals have been employed to teach and learn proper behaviour in a particular sacred ceremony of the Cheŵa people which takes place in celebration of womanhood: Chinamwali.

A fine structural localization of the non-specific cholinesterase activity in glomerular nerve formations (endings).

Science.gov (United States)

Dubový, P

1990-01-01

Snout glabrous skin (rhinarium) of the cat is innervated not only by typical simple lamellar corpuscles but also glomerular formations. In contrast to simple lamellar corpuscles, glomerular nerve formations are located away the dermal papillae. In cross sections, glomerular nerve formation consists of several axonal profiles enveloped by 1-2 cytoplasmic lamellae of Schwann cells. The space among them is filled by collagenous microfibrils and the basal lamina-like material. Capsule was composed from fibroblast-like cells without definite basal lamina. An electron-dense reaction product due to non-specific cholinesterase activity was associated with Schwann cells and their processes surrounding unmyelinated terminal portion of the sensory axons. Abundant reaction product was bound to the collagenous microfibrils and was deposited in extracellular matrix between Schwann cell processes. These results are further evidence for the presence of the non-specific cholinesterase molecules as integral component of the extracellular matrix in sensory corpuscles. On the basis of histochemical study two possible explanation are considered for functional involving of this enzyme in sensory nerve formations.

Serum aspirin esterase is strongly associated with glucose and lipids in healthy subjects: different association patterns in subjects with type 2 diabetes mellitus

Directory of Open Access Journals (Sweden)

Kotani Kazuhiko

2010-07-01

Full Text Available Abstract Background Aspirin esterase (AE activity can account for part of aspirin pharmacokinetics in the circulation, possibly being associated with the impairment of aspirin effectiveness as an inhibitor of platelet aggregation. Aims The study was aimed at investigating the correlations of serum AE activity with cholinesterase (ChE and metabolic variables in healthy subjects in comparison to subjects with type 2 diabetes mellitus (T2DM. Methods In cardiovascular disease-free T2DM subjects and healthy controls, the AE activity levels and/or the correlation patterns between AE and the other variables were analyzed. Results Neither AE nor ChE activities were higher in the subjects with T2DM. Serum AE activity strongly correlated with ChE as well as glucose/lipids variables such as total cholesterol and triglyceride in healthy subjects, while the correlations between AE and glucose/lipids variables were not present in T2DM subjects. Conclusions These data may reflect the pathophysiological changes between healthy and T2DM subjects. Our data may thus provide the basis for future studies to unravel the mechanisms.

L’immaginazione al lavoro. Che cosa e come conosciamo dal romanzo

Directory of Open Access Journals (Sweden)

Gianluca Consoli

2011-12-01

Full Text Available L’articolo delinea i fondamenti di un’epistemologia del romanzo, rispondendo alle domande di base: che cosa e come possiamo conoscere attraverso il romanzo. A partire dalla definizione del romanzo come racconto di finzione, viene sviluppata  una posizione di cognitivismo radicale, per la quale il romanzo (a produce conoscenza modale; (b giustifica questa conoscenza in base al principio della verosimiglianza; (c favorisce l’apprendimento per esperienza in virtù dell’esemplificazione immaginativa. Le tesi proposte vengono corroborate in riferimento ai recenti dati sperimentali ottenuti dalle scienze cognitive, in particolare dalla psicologia cognitiva, sull’immaginazione, la finzione, la simulazione.

Evaluation of Antioxidant, Anti-cholinesterase, and Anti-inflammatory Effects of Culinary Mushroom Pleurotus pulmonarius.

Science.gov (United States)

Nguyen, Trung Kien; Im, Kyung Hoan; Choi, Jaehyuk; Shin, Pyung Gyun; Lee, Tae Soo

2016-12-01

Culinary mushroom Pleurotus pulmonarius has been popular in Asian countries. In this study, the anti-oxidant, cholinesterase, and inflammation inhibitory activities of methanol extract (ME) of fruiting bodies of P. pulmonarius were evaluted. The 1,1-diphenyl-2-picryl-hydrazy free radical scavenging activity of ME at 2.0 mg/mL was comparable to that of butylated hydroxytoluene, the standard reference. The ME exhibited significantly higher hydroxyl radical scavenging activity than butylated hydroxytoluene. ME showed slightly lower but moderate inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase than galantamine, a standard AChE inhibitor. It also exhibited protective effect against cytotoxicity to PC-12 cells induced by glutamate (10~100 µg/mL), inhibitory effect on nitric oxide (NO) production and inducible nitric oxide synthase protein expression in lipopolysaccharide-stimulated RAW 264.7 macrophages, and carrageenan-induced paw edema in a rat model. High-performance liquid chromatography analysis revealed the ME of P. pulmonarius contained at least 10 phenolic compounds and some of them were identified by the comparison with known standard phenolics. Taken together, our results demonstrate that fruiting bodies of P. pulmonarius possess antioxidant, anti-cholinesterase, and inflammation inhibitory activities.

Pesticides and brain cancer linked in orchard farmers of Kashmir.

Science.gov (United States)

Bhat, Abdul Rashid; Wani, Muhammed Afzal; Kirmani, A R; Raina, T H

2010-10-01

The atmosphere of valley of Kashmir is ideal for fresh and dry fruit production. Millions of tons of pesticides, insecticides and fungicides (chemicals like chlorpyriphos, mancozeb, captan, dimethoate, phosalone, etc.) are being used by the orchard farmers to spray the plants, fruits and the leaves every year. The increasing trend in the incidence of primary malignant brain tumors in orchard farmers of Kashmir is alarming. To determine the relationship between the patients of primary malignant brain tumors and their occupation. Retrospectively case files along with death certificates of 432 patients of primary malignant brain tumors and 457 controls (non-tumor neurologic diseases), admitted for treatment simultaneously over a period of 4 years from January 2005 to December 2008, to the Department of Neurosurgery, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Kashmir, were studied. Follow-up and family contact was established. The serum cholinesterase activity was measured by kinetic/DGKC calorimetric method and ethylenediaminetetraacetic acid (EDTA) samples were sent to the laboratory. The results are expressed in U/l which is U/l×1000. The laboratory at SKIMS, Srinagar, and Dr Lal PathLabs at New Delhi used a reference range for serum cholinesterase as 3167-6333 U/l. Analysis revealed that 90.04% (389 out of 432) patients were orchard-farm workers, orchard residents and orchard playing children exposed to the high levels of multiple types of neurotoxic and carcinogenic (chlorpyriphos, dimethoate, mancozeb and captan) chemicals for more than 10-20 years. About 31.9% (124 out of 389) of these from both sexes were younger than 40 years beginning exposure at an early age and had higher (orchard-related 389 patients had high grade tumors as compared to the non-pesticide tumors. Mortality in pesticide exposed tumors was 12%. Higher levels of SCE were found in 31.9% (124 out of 389) patients and decreased levels in only 45.3% (176 out of 389) orchard

Different Cholinesterase Inhibitor Effects on CSF Cholinesterases in Alzheimer Patients

Science.gov (United States)

Nordberg, Agneta; Darreh-Shori, Taher; Peskind, Elaine; Soininen, Hilkka; Mousavi, Malahat; Eagle, Gina; Lane, Roger

2014-01-01

Background The current study aimed to compare the effects of different cholinesterase inhibitors on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and protein levels, in the cerebrospinal fluid (CSF) of Alzheimer disease (AD) patients. Methods and Findings AD patients aged 50–85 years were randomized to open-label treatment with oral rivastigmine, donepezil or galantamine for 13 weeks. AChE and BuChE activities were assayed by Ellman’s colorimetric method. Protein levels were assessed by enzyme-linked immunosorbent assay (ELISA). Primary analyses were based on the Completer population (randomized patients who completed Week 13 assessments). 63 patients were randomized to treatment. Rivastigmine was associated with decreased AChE activity by 42.6% and decreased AChE protein levels by 9.3%, and decreased BuChE activity by 45.6% and decreased BuChE protein levels by 21.8%. Galantamine decreased AChE activity by 2.1% and BuChE activity by 0.5%, but increased AChE protein levels by 51.2% and BuChE protein levels by10.5%. Donepezil increased AChE and BuChE activities by 11.8% and 2.8%, respectively. Donepezil caused a 215.2%increase in AChE and 0.4% increase in BuChE protein levels. Changes in mean AChE-Readthrough/Synaptic ratios, which might reflect underlying neurodegenerative processes, were 1.4, 0.6, and 0.4 for rivastigmine, donepezil and galantamine, respectively. Conclusion The findings suggest pharmacologically-induced differences between rivastigmine, donepezil and galantamine. Rivastigmine provides sustained inhibition of AChE and BuChE, while donepezil and galantamine do not inhibit BuChE and are associated with increases in CSF AChE protein levels. The clinical implications require evaluation. PMID:19199870

De novo amplification within a silent human cholinesterase gene in a family subjected to prolonged exposure to organophosphorus insecticides

International Nuclear Information System (INIS)

Prody, C.A.; Dreyfus, P.; Soreq, H.; Zamir, R.; Zakut, H.

1989-01-01

A 100-fold DNA amplification in the CHE gene, coding for serum butyrylcholinesterase (BtChoEase), was found in a farmer expressing silent CHE phenotype. Individuals homozygous for this gene display a defective serum BtChoEase and are particularly vulnerable to poisoning by agricultural organophosphorus insecticides, to which all members of this family had long been exposed. DNA blot hybridization with regional BtChoEase cDNA probes suggested that the amplification was most intense in regions encoding central sequences within BtChoEase cDNA, whereas distal sequences were amplified to a much lower extent. This is in agreement with the onion skin model, based on amplification of genes in cultured cells and primary tumors. The amplification was absent in the grandparents but present at the same extent in one of their sons and in a grandson, with similar DNA blot hybridization patterns. In situ hybridization experiments localized the amplified sequences to the long arm of chromosome 3, close to the site where the authors previously mapped the CHE gene. Altogether, these observations suggest that the initial amplification event occurred early in embryogenesis, spermatogenesis, or oogenesis, where the CHE gene is intensely active and where cholinergic functioning was indicated to be physiologically necessary. These findings demonstrate a de novo amplification in apparently healthy individuals within an autosomal gene producing a target protein to an inhibitor

New pharmacological approaches to the cholinergic system: an overview on muscarinic receptor ligands and cholinesterase inhibitors.

Science.gov (United States)

Greig, Nigel H; Reale, Marcella; Tata, Ada M

2013-08-01

The cholinergic system is expressed in neuronal and in non-neuronal tissues. Acetylcholine (ACh), synthesized in and out of the nervous system can locally contribute to modulation of various cell functions (e.g. survival, proliferation). Considering that the cholinergic system and its functions are impaired in a number of disorders, the identification of new pharmacological approaches to regulate cholinergic system components appears of great relevance. The present review focuses on recent pharmacological drugs able to modulate the activity of cholinergic receptors and thereby, cholinergic function, with an emphasis on the muscarinic receptor subtype, and additionally covers the cholinesterases, the main enzymes involved in ACh hydrolysis. The presence and function of muscarinic receptor subtypes both in neuronal and non-neuronal cells has been demonstrated using extensive pharmacological data emerging from studies on transgenic mice. The possible involvement of ACh in different pathologies has been proposed in recent years and is becoming an important area of study. Although the lack of selective muscarinic receptor ligands has for a long time limited the definition of therapeutic treatment based on muscarinic receptors as targets, some muscarinic ligands such as cevimeline (patents US4855290; US5571918) or xanomeline (patent, US5980933) have been developed and used in pre-clinical or in clinical studies for the treatment of nervous system diseases (Alzheimer' and Sjogren's diseases). The present review focuses on the potential implications of muscarinic receptors in different pathologies, including tumors. Moreover, the future use of muscarinic ligands in therapeutic protocols in cancer therapy will be discussed, considering that some muscarinic antagonists currently used in the treatment of genitourinary disease (e.g. darifenacin, patent, US5096890; US6106864) have also been demonstrated to arrest tumor progression in nude mice. The involvement of muscarinic

A step toward the reactivation of aged cholinesterases-crystal structure of ligands binding to aged human butyrylcholinesterase

NARCIS (Netherlands)

Wandhammer, M.; Koning, M. de; Grol, M. van; Loiodice, M.; Saurel, L.; Noort, D.; Goeldner, M.; Nachon, F.

2013-01-01

Organophosphorus nerve agents irreversibly inhibit cholinesterases. Phosphylation of the catalytic serine can be reversed by the mean of powerful nucleophiles like oximes. But the phosphyl adduct can undergo a rapid spontaneous reaction leading to an aged enzyme, i.e., a conjugated enzyme that is no

Ivermectin resistant and susceptible third-stage larvae of Haemonchus contortus: cholinesterase and phosphatase activities

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Consuelo Giménez-Pardo

2004-03-01

Full Text Available Cholinesterase and acid phosphatase (AP, but not alkaline phosphatase activities, were detected in cytosolic and membrane-bound fractions of ivermectin resistant and susceptible Haemonchus contortus infective-stage larvae. Some differences in acetylcholinesterase activity of cytosolic fractions and in the AP activity of these fractions as well as in the response to AP inhibitors by membrane-bound fractions were detected. Data are discussed.

Assessment of biological effects of pollutants in a hyper eutrophic tropical water body, Lake Beira, Sri Lanka using multiple biomarker responses of resident fish, Nile tilapia (Oreochromis niloticus).

Science.gov (United States)

Pathiratne, Asoka; Pathiratne, K A S; De Seram, P K C

2010-08-01

Biomarkers measured at the molecular and cellular level in fish have been proposed as sensitive "early warning" tools for biological effect measurements in environmental quality assessments. Lake Beira is a hypertrophic urban water body with a complex mixture of pollutants including polycyclic aromatic hydrocarbons (PAHs) and Microcystins. In this study, a suite of biomarker responses viz. biliary fluorescent aromatic compounds (FACs), hepatic ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST), brain and muscle cholinesterases (ChE), serum sorbitol dehydrogenase (SDH), and liver histology of Oreochromis niloticus, the dominant fish inhabiting this tropical Lake were evaluated to assess the pollution exposure and biological effects. Some fish sampled in the dry periods demonstrated prominent structural abnormalities in the liver and concomitant increase in serum SDH and reduction in hepatic GST activities in comparison to the control fish and the fish sampled in the rainy periods. The resident fish with apparently normal liver demonstrated induction of hepatic EROD and GST activities and increase in biliary FACs irrespective of the sampling period indicating bioavailability of PAHs. Muscle ChE activities of the resident fish were depressed significantly indicating exposure to anticholinesterase substances. The results revealed that fish populations residing in this Lake is under threat due to the pollution stress. Hepatic abnormalities in the fish may be mainly associated with the pollution stress due to recurrent exposure to PAHs and toxigenic Microcystis blooms in the Lake.

Assay techniques for detection of exposure to sulfur mustard, cholinesterase inhibitors, sarin, soman, GF, and cyanide. Technical bulletin

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-05-01

This technical bulletin provides analytical techniques to identify toxic chemical agents in urine or blood samples. It is intended to provide the clinician with laboratory tests to detect exposure to sulfur mustard, cholinesterase inhibitors, sarin, soman, GF, and cyanide.

Targeting neurotrophic factors and their receptors, but not cholinesterase or neurotransmitter, in the neurotoxicity of TDCPP in Chinese rare minnow adults (Gobiocypris rarus)

International Nuclear Information System (INIS)

Yuan, Lilai; Li, Jiasu; Zha, Jinmiao; Wang, Zijian

2016-01-01

Organophosphate flame retardants (OPFRs) have been detected at high concentrations in various environmental and biotic samples, but little is known about their toxicity. In this study, the potential neurotoxicity of three OPFRs (TCEP, TDCPP, and TPP) and Chlorpyrifos (CPF, an organophosphate pesticide) were compared in Chinese rare minnow using an acute toxicity test and a 21-day fish assay. The acute test demonstrated significant inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by CPF. Although significant AChE inhibition at high concentration of TPP was also observed, none of the OPFRs had effects similar to CPF on these enzymes, indicating that their acute toxicities to Chinese rare minnow may be unrelated to cholinesterase inhibition. In addition, the 21-day fish assay with TDCPP demonstrated no significant effects on cholinesterase activities or neurotransmitter levels. Nonetheless, this OPFR exhibited widespread effects on the neurotrophic factors and their receptors (e.g., ntf3, ntrk1, ntrk2, ngfr, and fgf2, fgf11, fgf22, fgfr4), indicating that TDCPP or other OPFRs may elicit neurological effects by targeting neurotrophic factors and their receptors in Chinese rare minnow. - Highlights: • Significant inhibition of AChE and BChE activities by CPF was observed. • None of the OPFRs had similar effects on the cholinesterase like the CPF. • TDCPP showed significant effects on the neurotrophic factor genes in rare minnow. - Although none of the tested OPFRs showed any significant effects on cholinesterase activities and neurotransmitter levels, TDCPP did elicit widespread effects on neurotrophic factor genes.

Tempi che cambiano, luoghi che si trasformano: i mutamenti nei nuraghi fra l’età del Bronzo ed il Primo Ferro

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Mauro Perra

2017-01-01

Full Text Available Riassunto: Il lungo percorso della Civiltà Nuragica, compreso fra XVII e X-IX secolo a.C., si caratterizza come un’epoca di grandi trasformazioni che si susseguono nel tempo e lasciano visibili tracce in un paesaggio mutevole, come in un succedersi di macroscopiche unità stratigrafiche. Si trasformano profondamente così non solo i monumenti ed il paesaggio, ma anche le stesse strutture sociali e politiche delle comunità nuragiche fino alla trasfigurazione del ricordo in mito nei centri cerimoniali o santuari. Abstract: The long trajectory of the Nuragic civilisation (17th - 10th/9th centuries B.C. is characterised by a succession of dramatic changes leaving visible traces in a varying landscape, like stratigraphy on a regional scale. These changes affect not only the Nuragic monuments and landscape but also the social and political institutions of Nuragic communities, culminating in a transfiguration of memory and a new mythology apparent in ceremonial centres and sanctuaries.

Inhibition of cholinesterase by essential oil from food plant.

Science.gov (United States)

Chaiyana, Wantida; Okonogi, Siriporn

2012-06-15

Inhibition of cholinesterase has attracted much attention recently because of its potential for the treatment of Alzheimer's disease. In this work, the anticholinesterase activities of plant oils were investigated using Ellman's colorimetric method. The results indicate that essential oils obtained from Melissa officinalis leaf and Citrus aurantifolia leaf showed high acetylcholinesterase and butyrylcholinesterase co-inhibitory activities. C. aurantifolia leaf oil revealed in this study has an IC(50) value on acetylcholinesterase and butyrylcholinesterase of 139 ± 35 and 42 ± 5 μg/ml, respectively. GC/MS analysis revealed that the major constituents of C. aurantifolia leaf oil are monoterpenoids including limonene, l-camphor, citronellol, o-cymene and 1,8-cineole. Copyright © 2012 Elsevier GmbH. All rights reserved.

Cholinesterase as inflammatory markers in a experimental infection by Trypanosoma evansi in rabbits

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Márcio M. Costa

2012-12-01

Full Text Available The aim of this study is to evaluate the role of cholinesterases as an inflammatory marker in acute and chronic infection by Trypanosoma evansi in rabbits experimentally infected. Twelve adult female New Zealand rabbits were used and divided into two groups with 6 animals each: control group (rabbits 1-6 and infected group (rabbits 7-12. Infected group received intraperitoneally 0.5 mL of blood from a rat containing 108 parasites per animal. Blood samples used for cholinesterases evaluation were collected on days 0, 2, 7, 12, 27, 42, 57, 87, 102 and 118 days post-inoculation (PI. Increased activity (P0.05 was observed in the encephalic structures. The increased activities of AChE and BChE probably have a pro-inflammatory purpose, attempting to reduce the concentration of acetylcholine, a neurotransmitter which has an anti-inflammatory property. Therefore, cholinesterase may be inflammatory markers in infection with T. evansi in rabbits.O objetivo do presente estudo é avaliar o papel das colinesterases como marcadores inflamatórios nas fases aguda e crônica da infecção por T. evansi em coelhos infectados experimentalmente. Foram utilizados 12 coelhos adultos, fêmeas, da raça Nova Zelândia, divididos em dois grupos: um grupo controle, com seis animais (coelhos 1-6, e um grupo infectado, com seis animais (coelhos 7-12. Os animais pertencentes ao grupo infectados receberam, pela via intraperitoneal, 0,5 mL de sangue de rato contendo 108 tripanossomas por animal. Amostras do sangue utilizado para avaliação das colinesterases foram coletadas nos dias 0, 2, 7, 12, 27, 42, 57, 87, 102 e 118 pós-inoculação (PI. Aumento (P0,05 foi observada nas estruturas encefálicas. O aumento de atividade da AChE e BChE provavelmente tenha finalidade pró-inflamatória, a fim de reduzir as concentrações de acetilcolina, neurotransmissor que apresenta propriedade anti-inflamatória. Portanto, as colinesterases podem ser marcadores inflamatórios na infec

Synthesis, Molecular Modelling and Biological Evaluation of Novel Heterodimeric, Multiple Ligands Targeting Cholinesterases and Amyloid Beta

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Michalina Hebda

2016-03-01

Full Text Available Cholinesterases and amyloid beta are one of the major biological targets in the search for a new and efficacious treatment of Alzheimer’s disease. The study describes synthesis and pharmacological evaluation of new compounds designed as dual binding site acetylcholinesterase inhibitors. Among the synthesized compounds, two deserve special attention—compounds 42 and 13. The former is a saccharin derivative and the most potent and selective acetylcholinesterase inhibitor (EeAChE IC50 = 70 nM. Isoindoline-1,3-dione derivative 13 displays balanced inhibitory potency against acetyl- and butyrylcholinesterase (BuChE (EeAChE IC50 = 0.76 μM, EqBuChE IC50 = 0.618 μM, and it inhibits amyloid beta aggregation (35.8% at 10 μM. Kinetic studies show that the developed compounds act as mixed or non-competitive acetylcholinesterase inhibitors. According to molecular modelling studies, they are able to interact with both catalytic and peripheral active sites of the acetylcholinesterase. Their ability to cross the blood-brain barrier (BBB was confirmed in vitro in the parallel artificial membrane permeability BBB assay. These compounds can be used as a solid starting point for further development of novel multifunctional ligands as potential anti-Alzheimer’s agents.

Effects of Kapton Sample Cell Windows on the Detection Limit of Smectite: Implications for CheMin on the Mars Science Laboratory Mission

Science.gov (United States)

Achilles, C. N.; Ming, Douglas W.; Morris, R. V.; Blake, D. F.

2012-01-01

The CheMin instrument on the Mars Science Laboratory (MSL) rover Curiosity is an X-ray diffraction (XRD) and X-ray fluorescence (XRF) instrument capable of providing the mineralogical and chemical compositions of rocks and soils on the surface of Mars. CheMin uses a microfocus X-ray tube with a Co target, transmission geometry, and an energy-discriminating X-ray sensitive CCD to produce simultaneous 2-D XRD patterns and energy-dispersive X-ray histograms from powdered samples. CheMin has two different window materials used for sample cells -- Mylar and Kapton. Instrument details are provided elsewhere. Fe/Mg-smectite (e.g., nontronite) has been identified in Gale Crater, the MSL future landing site, by CRISM spectra. While large quantities of phyllosilicate minerals will be easily detected by CheMin, it is important to establish detection limits of such phases to understand capabilities and limitations of the instrument. A previous study indicated that the (001) peak of smectite at 15 Ang was detectable in a mixture of 1 wt.% smectite with olivine when Mylar is the window material for the sample cell. Complications arise when Kapton is the window material because Kapton itself also has a diffraction peak near 15 Ang (6.8 deg 2 Theta). This study presents results of mineral mixtures of smectite and olivine to determine smectite detection limits for Kapton sample cells. Because the intensity and position of the smectite (001) peak depends on the hydration state, we also analyzed mixtures with "hydrated" and "dehydrated"h smectite to examine the effects of hydration state on detection limits.

Plasma cholinesterase inhibition in the clay-colored robin (Turdus grayi) exposed to diazinon in maradol papaya crops in Yucatan, Mexico

Science.gov (United States)

Cobos, V.M.; Mora, M.A.; Escalona, G.

2006-01-01

The use of organophosphorous pesticides in agriculture can result in intoxication of birds foraging in sprayed crops. Effects on birds resulting from pesticide intoxication are varied and include behavioral and reproductive effects, including death. One widely used insecticide in Maradol papaya crops is diazinon which has been associated with various incidents of intoxication and death of wild birds. The objective of this study was to evaluate the impact of diazinon application to papaya crops on plasma cholinesterase activity of the clay-colored robin (Turdus grayi). We captured clay-colored robins foraging in a papaya crop the following day after the field had been sprayed with diazinon at a dose of 1.5 kg/ha during March and May, respectively. We took a blood sample from the brachialis vein of the birds captured and measured plasma enzymatic activity. The plasma samples from birds used as controls were taken during the same time period and were analyzed in a similar way. Enzymatic activity of males was greater than that of females (53,52%) and mean cholinesterase inhibition was 49.43%. Cholinesterase inhibition was greater during May than in March probably due to more continuous exposure and ingestion of the insecticide through food and possible absorption through the skin. This degree of enzymatic inhibition is possibly affecting the behavior of the clay-colored robin and could result in death in severe cases.

A new method to characterize the kinetics of cholinesterases inhibited by carbamates.

Science.gov (United States)

Xiao, Qiaoling; Zhou, Huimin; Wei, Hong; Du, Huaqiao; Tan, Wen; Zhan, Yiyi; Pistolozzi, Marco

2017-09-10

The inhibition of cholinesterases (ChEs) by carbamates includes a carbamylation (inhibition) step, in which the drug transfers its carbamate moiety to the active site of the enzyme and a decarbamylation (activity recovery) step, in which the carbamyl group is hydrolyzed from the enzyme. The carbamylation and decarbamylation kinetics decide the extent and the duration of the inhibition, thus the full characterization of candidate carbamate inhibitors requires the measurement of the kinetic constants describing both steps. Carbamylation and decarbamylation rate constants are traditionally measured by two separate set of experiments, thus making the full characterization of candidate inhibitors time-consuming. In this communication we show that by the analysis of the area under the inhibition-time curve of cholinesterases inhibited by carbamates it is possible to calculate the decarbamylation rate constant from the same data traditionally used to characterize only the carbamylation kinetics, therefore it is possible to obtain a full characterization of the inhibition with a single set of experiments. The characterization of the inhibition kinetics of human and dog plasma butyrylcholinesterase and of human acetylcholinesterase by bambuterol and bambuterol monocarbamate enantiomers was used to demonstrate the validity of the approach. The results showed that the proposed method provides reliable estimations of carbamylation and decarbamylation rate constants thus representing a simple and useful approach to reduce the time required for the characterization of carbamate inhibitors. Copyright © 2017 Elsevier B.V. All rights reserved.

Il mondo secondo la fisica quantistica segreti e meraviglie della scienza che sta cambiando la nostra vita

CERN Document Server

Fracas, Fabio

2017-01-01

Questo libro è un'avventura esclusiva e affascinante. Un viaggio, anche nel tempo, alla scoperta di qualcosa di nuovo e di straordinario: la Fisica Quantistica, nelle sue logiche, nelle sue potenzialità, nelle sue applicazioni e nei suoi possibili sviluppi. All'interno del volume vengono ricostruiti passo dopo passo i momenti fondamentali del pensiero quantistico, le questioni su cui si sono interrogati i più grandi scienziati degli ultimi decenni, e i diversi contesti nei quali si sono evoluti i principali modelli della Meccanica Quantistica. Sullo sfondo delle ricerche più attuali - come per esempio quella sulle onde gravitazionali che ha portato al Nobel per la Fisica 2017 -, vengono indagati anche i rapporti esistenti fra Fisica Quantistica, Relatività Einsteiniana e Teoria delle Stringhe. Inoltre, fra i tanti temi trattati nelle sue pagine, trovano spazio persino le incredibili ricadute che gli studi sulla Fisica Quantistica stanno avendo negli ambiti della medicina e delle ricerche sul cervello e s...

Acquisition and reinstatement of ethanol-induced conditioned place preference in rats: Effects of the cholinesterase inhibitors donepezil and rivastigmine.

Science.gov (United States)

Gawel, Kinga; Labuz, Krzysztof; Gibula-Bruzda, Ewa; Jenda, Malgorzata; Marszalek-Grabska, Marta; Silberring, Jerzy; Kotlinska, Jolanta H

2016-07-01

The present study examined the influence of the cholinesterase inhibitors donepezil (a selective inhibitor of acetylcholinesterase) and rivastigmine (also an inhibitor of butyrylcholinesterase) on the acquisition and reinstatement of ethanol-induced conditioned place preference (CPP) in rats. Before the CPP procedure, animals received a single injection of ethanol (0.5 g/kg, 10% w/v, intraperitoneally [i.p.]) for 15 days. The ethanol-induced CPP (biased method) was developed by four injections of ethanol (0.5 g/kg, 10% w/v, i.p.) every second day. Control rats received saline instead of ethanol. Donepezil (0.5, 1 or 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5 or 1 mg/kg, i.p.) were administered before ethanol during conditioning or before the reinstatement of ethanol-induced CPP. The cholinesterase inhibitors were equally effective in increasing (dose dependently) the acquisition of ethanol-induced CPP. Furthermore, priming injections of both inhibitors reinstated (cross-reinstatement) the ethanol-induced CPP with similar efficacy. These effects of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist, but not by scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. Thus, our results show that the cholinergic system is involved in the reinforcing properties of ethanol, and nicotinic acetylcholine receptors play an important role in the relapse to ethanol-seeking behaviour. © The Author(s) 2016.

The reactivation effect of pralidoxime in human blood on parathion and paraoxon–induced cholinesterase inhibition

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Mahvash Jafari

2006-03-01

Full Text Available In this investigation the reactivation of cholinesterases by pralidoxime in parathion and paraoxon intoxication in plasma and erythrocytes were studied. For this purpose, human plasma and erythrocytes were incubated with various concentrations of parathion (0.1-10 µM and paraoxon (0.03-0.3 µM at 37 oC for 10 min. Then, pralidoxime (10-300 µM was added to the samples and incubated for 10 min before cholinesterases assay. The results showed that effects of parathion and paraoxon were dose dependent. These agents inhibited more than 85% of butyrylcholinesterase (BChE and acetylcholinesterase (AChE activity and the inhibitory effect of paraoxon was 10 times more than parathion. BChE activity was significantly higher than the control at 100 µM of pralidoxime and it reduced inhibitory effects of parathion to less than 50% and of paraoxon to 42% of control. When pralidoxime (10 µM was added to erythrocytes, the inhibitory effects of two organophosphates were reduced to less than 15%. At higher concentrations of pralidoxime (>100 µM, both BChE and AChE activities were inhibited.

Rachunek dochodów i wydatków budżetu jednostki samorządu terytorialnego na przykładzie gminy Chełmiec w latach 2011-2013

OpenAIRE

Rodak, Anna

2015-01-01

Przedłożona praca ma na celu wskazanie źródeł i struktury dochodów budżetowych oraz charakteru wydatkowania środków budżetowych gminy Chełmiec, a także dokonanie rzetelnej oceny sytuacji finansowej wymienionej powyżej jednostki. Analiza budżetu obejmuje zakres czasowy od 2011 do 2013 roku. Szczegółowe pytania, na które starano się w niniejszej pracy odpowiedzieć są następujące: Czy gmina Chełmiec jest gospodarna w wykorzystywaniu środków budżetowych? oraz jak gmina Chełmiec mając do dyspozycj...

[Reference values for erythrocyte cholinesterase activity in the working population of Antioquia, Colombia, according to the Michel and EQM techniques].

Science.gov (United States)

Carmona-Fonseca, Jaime

2003-11-01

To establish reference values for erythrocyte cholinesterase (EC 3.1.1.7) activity for the active working population of two regions of the department of Antioquia, Colombia, that are located at different altitudes above sea level. We took representative samples from populations of active working persons 18 to 59 years old from two regions in the department of Antioquia: (1) the Aburrá Valley (1 540 m above sea level) and (2) the near east of the department (2 150 m above sea level). We excluded workers who were using cholinesterase-inhibiting substances in their work or at home, those who had a disease that altered their cholinesterase levels, and those who said they were not in good health. We measured the erythrocyte cholinesterase activity using two methods: (1) the Michel method and (2) the EQM method (EQM Research, Cincinnati, Ohio, United States of America). We carried out the measurements with 827 people, 415 from the Aburrá Valley and 412 from the near east region. We compared proportions using the chi-square test and Fisher's exact test. We utilized the Student's t test for independent samples to compare two averages. To simultaneously compare three or more averages, analysis of variance was used, followed by the Newman-Keuls multiple-range test. When the variables were not normally distributed or when the variances were not homogeneous, Kruskal-Wallis nonparametric analysis of variance was used to compare the medians. Three computer software programs were used in the statistical analysis: SPSS 9.0, SGPlus 7.1, and Epi Info 6.04. In all the statistical tests the level of significance was set at P EQM method was 35.21 U/g hemoglobin (95% CI: 34.82 to 35.60). With the Michel method: (1) the enzymatic activity differed significantly between the two regions, according to the Newman-Keuls test; (2) within each region, the enzymatic activity was significantly higher among males than among females, according to the Newman-Keuls test; and (3) in none of the

Aluminium sulfate exposure: A set of effects on hydrolases from brain, muscle and digestive tract of juvenile Nile tilapia (Oreochromis niloticus).

Science.gov (United States)

Oliveira, Vagne Melo; Assis, Caio Rodrigo Dias; Costa, Helane Maria Silva; Silva, Raquel Pereira Freitas; Santos, Juliana Ferreira; Carvalho, Luiz Bezerra; Bezerra, Ranilson Souza

2017-01-01

Aluminium is a major pollutant due to its constant disposal in aquatic environments through anthropogenic activities. The physiological effects of this metal in fish are still scarce in the literature. This study investigated the in vivo and in vitro effects of aluminium sulfate on the activity of enzymes from Nile tilapia (Oreochromis niloticus): brain acetylcholinesterase (AChE), muscle cholinesterases (AChE-like and BChE-like activities), pepsin, trypsin, chymotrypsin and amylase. Fish were in vivo exposed during 14days when the following experimental groups were assayed: control group (CG), exposure to Al 2 (SO 4 ) 3 at 1μg·mL -1 (G1) and 3μg·mL -1 (G3) (concentrations compatible with the use of aluminium sulfate as coagulant in water treatment). In vitro exposure was performed using animals of CG treatment. Both in vivo and in vitro exposure increased cholinesterase activity in relation to controls. The highest cholinesterase activity was observed for muscle BChE-like enzyme in G3. In contrast, the digestive enzymes showed decreased activity in both in vivo and in vitro exposures. The highest inhibitory effect was observed for pepsin activity. The inhibition of serine proteases was also quantitatively analyzed in zymograms using pixel optical densitometry as area under the peaks (AUP) and integrated density (ID). These results suggest that the inhibition of digestive enzymes in combination with activation of cholinesterases in O. niloticus is a set of biochemical effects that evidence the presence of aluminium in the aquatic environment. Moreover, these enzymatic alterations may support further studies on physiological changes in this species with implications for its neurological and digestive metabolisms. Copyright © 2016 Elsevier Inc. All rights reserved.

Cholinesterase activity in blood and pesticide presence in sweat as biomarkers of children`s environmental exposure to crop protection chemicals

Directory of Open Access Journals (Sweden)

Lucyna Kapka-Skrzypczak

2015-09-01

Altogether, the study indicated that cholinesterase activity is a sensitive marker of the children’s environmental exposure to pesticides, whereas sweat patches are useful devices for collecting samples to be analysed for the presence of the pesticides.

[COMPARATIVE SENSITIVITY OF CHOLINESTERASES IN VERTEBRATES AND INVERTEBRATES TO HIGHLY SPECIFIC ORGANOPHOSPHORUS INHIBITORS DIISOPROPYL FLUOROPHOSPHATE (DFP) AND (2-ETHOXYMETHYL PHOSPHORYL THIOETHYL) ETHYL (METHYL) SULPHONIUM SULPHOMETHYLAT (GD-42)].

Science.gov (United States)

Basova, N E; Kormilitsyn, B N; Perchenok, A Yu; Rozengart, E V; Saakov, V S; Suvorov, A A

2015-01-01

The review presents data on comparative reactivity of 68 cholinesterase preparation from various organs and tissues in a number of vertebrates and invertebrates based on sensitivity to two highly specific and most studied organophosphorus inhibitors--diisopropyl fluorophosphates (DFP) and (2-ethoxymethyl phosphoryl thioethyl) ethyl (methyl) sulphonium sulphomethylat (GD-42). Analysis of these data suggests a great diversity in enzymologic characteristics of cholinesterase preparation in representatives of vertebrates and invertebrates, this variety observed even for closely related enzymes in animals of almost the same level of development.

New advances in pharmacological approaches to the cholinergic system: an overview on muscarinic receptor ligands and cholinesterase inhibitors

Science.gov (United States)

Greig, Nigel H.; Reale, Marcella; Tata, Ada Maria

2016-01-01

The cholinergic system is expressed in neuronal and in non-neuronal tissues. Acetylcholine (ACh), synthesized in and out of the nervous system can locally contribute to modulation of various cell functions (e.g. survival, proliferation). Considering that the cholinergic system and its functions are impaired in a number of disorders, the identification of new pharmacological approaches to regulate cholinergic system components appears of great relevance. The present review focuses on recent pharmacological drugs able to modulate the activity of cholinergic receptors and thereby, cholinergic function, with an emphasis on the muscarinic receptor subtype, and additionally covers the cholinesterases, the main enzymes involved in ACh hydrolysis. The presence and function of muscarinic receptor subtypes both in neuronal and non-neuronal cells has been demonstrated using extensive pharmacological data emerging from studies on transgenic mice. The possible involvement of ACh in different pathologies has been proposed in recent years and is becoming an important area of study. Although the lack of selective muscarinic receptor ligands has for a long time limited the definition of therapeutic treatment based on muscarinic receptors as targets, some muscarinic ligands such as cevimeline (patents US4855290; US5571918) or xanomeline (patent, US5980933) have been developed and used in pre-clinical or in clinical studies for the treatment of nervous system diseases (Alzheimer’ and Sjogren’s diseases). The present review focuses on the potential implications of muscarinic receptors in different pathologies, including tumors. Moreover, the future use of muscarinic ligands in therapeutic protocols in cancer therapy will be discussed, considering that some muscarinic antagonists currently used in the treatment of genitourinary disease (e.g. darifenacin, patent, US5096890; US6106864) have also been demonstrated to arrest tumor progression in nude mice. The involvement of muscarinic

[Isomeric derivatives of lupinine and epilupinine--organophosphorus inhibitors of cholinesterases].

Science.gov (United States)

Basova, N E; Kormilitsyn, B N; Perchenok, A Iu; Rosengart, E V; Saakov, V S; Suvorov, A A

2012-01-01

The isomeric-structure analysis data of anticholinesterase action of organophosphorous inhibitors with similar structure help in the search of specific effectors and detection of differences in reactivity of various animals' enzymes. This study compared the data of efficacy in respect of 4 mammal and 5 arthropoda cholinesterase preparations for 26 quinolizidine inhibitors, which molecules contain both the isomeric unbranched and branched alkoxyl radicals in the phosphoryl group, and the epimeric lupinine and epilupinine derivatives in the leaving group. The changes in the alkoxyl radical structure of inhibitor molecules act on their efficacy only with respect to the mammal enzymes ("group" inhibitor specificity). The differences between lupinine and epilupinine derivatives were revealed. Highly specific inhibitors of different enzymes were detected among the tested compounds.

Efficacy of fresh packed red blood transfusion in organophosphate poisoning.

Science.gov (United States)

Bao, Hang-Xing; Tong, Pei-Jian; Li, Cai-Xia; Du, Jing; Chen, Bing-Yu; Huang, Zhi-Hui; Wang, Ying

2017-03-01

The mortality rate caused by organophosphate (OP) poisoning is still high, even the standard treatment such as atropine and oxime improves a lot. To search for alternative therapies, this study was aimed to investigate the effects of packed red blood cell (RBC) transfusion in acute OP poisoning, and compare the therapeutic effects of RBCs at different storage times.Patients diagnosed with OP poisoning were included in this prospective study. Fresh RBCs (packed RBCs stored less than 10 days) and longer-storage RBCs (stored more than 10 days but less than 35 days) were randomly transfused or not into OP poisoning patients. Cholinesterase (ChE) levels in blood, atropine usage and durations, pralidoxime durations were measured.We found that both fresh and longer-storage RBCs (200-400 mL) significantly increased blood ChE levels 6 hours after transfusion, shortened the duration for ChE recovery and length of hospital stay, and reduced the usage of atropine and pralidoxime. In addition, fresh RBCs demonstrated stronger therapeutic effects than longer-storage RBCs.Packed RBCs might be an alternative approach in patients with OP poisoning, especially during early stages.

Adverse Drug Reactions Reported With Cholinesterase Inhibitors : An Analysis of 16 Years of Individual Case Safety Reports From VigiBase

NARCIS (Netherlands)

Kroeger, Edeltraut; Mouls, Marie; Wilchesky, Machelle; Berkers, Mieke; Carmichael, Pierre-Hugues; van Marum, Rob; Souverein, Patrick; Egberts, Toine; Laroche, Marie-Laure

2015-01-01

Background: No worldwide pharmacovigilance study evaluating the spectrum of adverse drug reactions (ADRs) induced by cholinesterase inhibitors (ChEI) in Alzheimer's disease has been conducted since their emergence on the market. Objective: To describe ChEI related ADRs in Alzheimer's disease

Effect of induced epilepsy on some biochemical parameters in female rats

Directory of Open Access Journals (Sweden)

J.S. H. Ali

2012-01-01

Full Text Available The activity of cholinesterase and some biochemical parameters of blood such as glucose, cholesterol and phospholipids were estimated in 52 epilepsy induced females of Wister albino rats. Animals of this experiment were divided into two groups, group (I regarded as control and group (II administrated subcutaneously by pentylenetetrazole 100mg/kg and divided in to three sub-groups according to the time of samples collection 3 hrs, 24 hrs and 1 week. The results revealed that epilepsy induction caused a significant inhibition of serum cholinesterase activity 3 hrs after induction while in the brain, the activity of cholinesterase was significantly increased after 24 hrs Serum glucose level was significantly elevated after 3 hrs and 24 hrs of induction, total cholesterol and phospholipids were not changed. From the results obtained in this study, it can be concluded that epilepsy caused significant changes in cholinesterase activity in brain and serum in addition to the glucose level in the serum.

Adverse Drug Reactions Reported With Cholinesterase Inhibitors: An Analysis of 16 Years of Individual Case Safety Reports From VigiBase

NARCIS (Netherlands)

Kroger, E.; Mouls, M.; Wilchesky, M.; Berkers, M.; Carmichael, P.H.; van Marum, R.J.; Souverein, P.; Egberts, T.; Laroche, M.L.

2015-01-01

Background: No worldwide pharmacovigilance study evaluating the spectrum of adverse drug reactions (ADRs) induced by cholinesterase inhibitors (ChEI) in Alzheimer’s disease has been conducted since their emergence on the market. Objective: To describe ChEI related ADRs in Alzheimer’s disease

Lithium blocks ethanol-induced modulation of protein kinases in the developing brain

International Nuclear Information System (INIS)

Chakraborty, Goutam; Saito, Mitsuo; Mao, Rui-Fen; Wang, Ray; Vadasz, Csaba; Saito, Mariko

2008-01-01

Lithium has been shown to be neuroprotective against various insults including ethanol exposure. We previously reported that ethanol-induced apoptotic neurodegeneration in the postnatal day 7 (P7) mice is associated with decreases in phosphorylation levels of Akt, glycogen synthase kinase-3β (GSK-3β), and AMP-activated protein kinase (AMPK), and alteration in lipid profiles in the brain. Here, P7 mice were injected with ethanol and lithium, and the effects of lithium on ethanol-induced alterations in phosphorylation levels of protein kinases and lipid profiles in the brain were examined. Immunoblot and immunohistochemical analyses showed that lithium significantly blocked ethanol-induced caspase-3 activation and reduction in phosphorylation levels of Akt, GSK-3β, and AMPK. Further, lithium inhibited accumulation of cholesterol ester (ChE) and N-acylphosphatidylethanolamine (NAPE) triggered by ethanol in the brain. These results suggest that Akt, GSK-3β, and AMPK are involved in ethanol-induced neurodegeneration and the neuroprotective effects of lithium by modulating both apoptotic and survival pathways

SYM1, l’ortologo di lievito del gene umano MPV17, codifica per una proteina indotta da stress che modula lo stato bioenergetico e morfogenetico del mitocondrio

OpenAIRE

Dallabona, Cristina

2010-01-01

Mutazioni nel gene MPV17 causano l’insorgenza di una forma epatocerebrale della sindrome da deplezione del DNA mitocondriale. MPV17 codifica per una piccola proteina idrofobica localizzata nella membrana mitocondriale interna con funzione sconosciuta. Per cercare di chiarire le basi molecolari che causano la patologia, abbiamo utilizzato il lievito S. cerevisiae come organismo modello grazie alla presenza di un ortologo di MPV17: SYM1. Abbiamo dimostrato che la proteina Sym1 è essenziale per ...

Electron microscopical study of non-specific cholinesterase activity in simple lamellar corpuscles of glabrous skin from cat rhinarium: a histochemical evidence for the presence of collagenase-sensitive molecular forms and their secretion.

Science.gov (United States)

Dubový, P

1989-01-01

The distribution of nCHE activity was studied histochemically in simple lamellar corpuscles (SLCs) of glabrous skin from cat rhinarium. The Schwann cells forming myelin sheaths in preterminal part of SCLs exhibited no positive reaction for nCHE activity. Prevalent reaction product was localized extracellularly in the inne core enveloping terminal portion of unmyelinated sensory axon. A dot-like shaped reaction product was deposited in the basal lamina of the inner core cells and their cytoplasmic lamellae or was scattered in enlarged interlamellar spaces. Only small amount of fine end product was found to be associated with the plasma membrane of inner core lamellae. Fine reaction product for nCHE activity was consistently localized in perinuclear and rER cisternae and saccules of the Golgi apparatus of inner core cells. Some vesicles around rER and the Golgi apparatus, ones beneath the plasma membrane, and tubular-like cisternal profiles oriented towards the surface contained nCHE end product, as well. The intracellular and extracellular localization of nCHE reaction product suggests that this enzyme behaves in cat SLCs as a secreted rather than as an integral membrane protein. A large amount of dot-like reaction product in the interlamellar spaces disappeared if the skin sections were treated with collagenase before incubation in the medium for histochemical detection of nCHE activity. The decrease of nCHE end product in SLCs of the skin sections after collagenase digestion was corroborated by means of light microdensitometer and electrometrical measurement. The histochemical detection and electrometrical measurement revealed that the majority of the reaction product in the interlamellar spaces of inner core corresponds with the nCHE molecules sensitive to collagenase treatment and they are probably counted among asymmetrical molecular forms.

“Nell’occhio che riscopre la luce”: tempo, Storia e memoria nella poesia di Salvatore Quasimodo

OpenAIRE

Alessandro Martini

2015-01-01

La riflessione sul rapporto dell’uomo con il tempo e con la storia percorre senza soluzione di continuità l’opera poetica di Salvatore Quasimodo. Spesso a disagio in una dimensione temporale fissa e definita, schiacciato tra dolore dell’esilio, insensatezza della guerra e crisi del dopoguerra, il poeta interroga gli evi passati e le ere future in cerca di un’armonia che appare il più delle volte sfuggente.

Crèche and School of the Staff Association: a programme for children from 2 to 4 year old

CERN Multimedia

Staff Association

2018-01-01

Find out how children between the ages of two to four and their families can benefit from the Staff Association Crèche and School programme. Classes for children aged between two and four years have been set-up to ensure the initial transition from home to school is as smooth as possible. Children attend mornings only and are welcomed by the same group of teaching staff throughout the week, allowing the children to establish a link between their home life and the crèche/school. The challenge of these classes is to offer the children a happy environment where they can feel emotionally secure, and the teaching staff can create a harmonious atmosphere allowing them to learn by moving, manipulating, exchanging, making mistakes… playing. Creativity takes a central role as it enables the child to express him or herself and increase their ability to handle their emotions constructively. According to Albert Einstein ‘Play is the highest form of research’. &nbs...

Design, synthesis and biological evaluation of benzo[e][1,2,4]triazin-7(1H)-one and [1,2,4]-triazino[5,6,1-jk]carbazol-6-one derivatives as dual inhibitors of beta-amyloid aggregation and acetyl/butyryl cholinesterase.

Science.gov (United States)

Catto, Marco; Berezin, Andrey A; Lo Re, Daniele; Loizou, Georgia; Demetriades, Marina; De Stradis, Angelo; Campagna, Francesco; Koutentis, Panayiotis A; Carotti, Angelo

2012-12-01

Alzheimer's disease (AD) 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. Two new chemical entities, the easily accessible heterocyclic scaffolds 1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (benzotriazinone I) and 2-phenyl-6H-[1,2,4]triazino[5,6,1-jk]carbazol-6-one (triazafluoranthenone II), were explored for their multitarget-directed inhibition of beta-amyloid (Aβ) fibrillization and acetyl- (AChE) and/or butyryl- (BChE) cholinesterase, three valuable targets for AD therapy. Introduction of appropriate amine substituents at positions 6 and 5 on scaffold I and II, respectively, allowed the preparation of a series of compounds that were tested as Aβ(1-40) aggregation and cholinesterase inhibitors. Potent inhibitors of Aβ self-aggregation were discovered and among them benzotriazinone 7 exhibited an outstanding IC(50) equal to 0.37 μM. Compounds bearing a basic amine linked to the heterocyclic scaffold through a linear alkyl chain of varying length also afforded good ChE inhibitors. In particular, benzotriazinone 24 and triazafluoranthenone 38 were endowed with an interesting multiple activity, the former displaying IC(50) values of 1.4, 1.5 and 1.9 μM on Aβ aggregation and AChE and BChE inhibition, respectively, and the latter showing IC(50) values of 1.4 and an outstanding 0.025 μM in the Aβ aggregation and BChE inhibition, respectively. Benzotriazinone 24 and triazafluoranthenone 29, selected owing to their suitable aqueous solubility and Aβ aggregation inhibition, were submitted to a time course kinetic assay followed with thioflavin T (ThT) spectrofluorimetry, circular dichroism (CD) and transmission electron microscopy (TEM). Experimental data indicated that 24 acted at a low concentration ratio (10 μM 24 vs. 50 μM Aβ), stabilizing the unstructured Aβ peptide and inhibiting fibrillogenesis, and that 29

Synthesis, pharmacology and molecular docking on multifunctional tacrine-ferulic acid hybrids as cholinesterase inhibitors against Alzheimer's disease.

Science.gov (United States)

Zhu, Jie; Yang, Hongyu; Chen, Yao; Lin, Hongzhi; Li, Qi; Mo, Jun; Bian, Yaoyao; Pei, Yuqiong; Sun, Haopeng

2018-12-01

The cholinergic hypothesis has long been a "polar star" in drug discovery for Alzheimer's disease (AD), resulting in many small molecules and biological drug candidates. Most of the drugs marketed for AD are cholinergic. Herein, we report our efforts in the discovery of cholinesterases inhibitors (ChEIs) as multi-target-directed ligands. A series of tacrine-ferulic acid hybrids have been designed and synthesised. All these compounds showed potent acetyl-(AChE) and butyryl cholinesterase(BuChE) inhibition. Among them, the optimal compound 10g, was the most potent inhibitor against AChE (electrophorus electricus (eeAChE) half maximal inhibitory concentration (IC 50 ) = 37.02 nM), it was also a strong inhibitor against BuChE (equine serum (eqBuChE) IC 50  = 101.40 nM). Besides, it inhibited amyloid β-protein self-aggregation by 65.49% at 25 μM. In subsequent in vivo scopolamine-induced AD models, compound 10g obviously ameliorated the cognition impairment and showed preliminary safety in hepatotoxicity evaluation. These data suggest compound 10g as a promising multifunctional agent in the drug discovery process against AD.

Ramalina capitata (Ach.) Nyl. acetone extract: HPLC analysis, genotoxicity, cholinesterase, antioxidant and antibacterial activity.

Science.gov (United States)

Zrnzevic, Ivana; Stankovic, Miroslava; Stankov Jovanovic, Vesna; Mitic, Violeta; Dordevic, Aleksandra; Zlatanovic, Ivana; Stojanovic, Gordana

2017-01-01

In the present investigation, effects of Ramalina capitata acetone extract on micronucleus distribution on human lymphocytes, on cholinesterase activity and antioxidant activity (by the CUPRAC method) were examined, for the first time as well as its HPLC profile. Additionally, total phenolic compounds (TPC), antioxidant properties (estimated via DPPH, ABTS and TRP assays) and antibacterial activity were determined. The predominant phenolic compounds in this extract were evernic, everninic and obtusatic acids. Acetone extract of R. capitata at concentration of 2 μg mL -1 decreased a frequency of micronuclei (MN) for 14.8 %. The extract reduces the concentration of DPPH and ABTS radicals for 21.2 and 36.1 % (respectively). Values for total reducing power (TRP) and cupric reducing capacity (CUPRAC) were 0.4624 ± 0.1064 μg ascorbic acid equivalents (AAE) per mg of dry extract, and 6.1176 ± 0.2964 μg Trolox equivalents (TE) per mg of dry extract, respectively. The total phenol content was 670.6376 ± 66.554 μg galic acid equivalents (GAE) per mg of dry extract. Tested extract at concentration of 2 mg mL -1 exhibited inhibition effect (5.2 %) on pooled human serum cholinesterase. The antimicrobial assay showed that acetone extract had inhibition effect towards Gram-positive strains. The results of manifested antioxidant activity, reducing the number of micronuclei in human lymphocytes, and antibacterial activity recommends R. capitata extract for further in vivo studies.

Enhancement of anti-cholinesterase activity of Zingiber cassumunar essential oil using a microemulsion technique.

Science.gov (United States)

Okonogi, S; Chaiyana, W

2012-10-01

The aim of the present study was to enhance the cholinesterase inhibitory activity of Zingiber cassumunar (ZC) oil using a microemulsion (ME) technique. Pseudoternary phase diagrams of the oil, water, and surfactant/co-surfactant mixture were constructed using a water titration method. Effects of co-surfactant, surfactant/co-surfactant ratio, ionic strength, and pH were examined by means of the microemulsion region which existed in the phase diagrams. The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were tested by Ellman's colorimetric assay. It was found that ZC oil possesses inhibitory activity against not only AChE but also BChE. Formulation of ZC oil as ME revealed that alkyl chain length and number of hydroxyl groups of co-surfactant exhibited a remarkable effect on the pseudoternary phase diagram. Longer alkyl chains and more hydroxyl groups gave smaller regions of MEs. Ionic strength also affected the ME region. However, the phase behavior was hardly influenced by pH. The suitable ZC oil ME was composed of Triton X-114 in combination with propylene glycol. The anti-cholinesterase activity of this ME was much higher than that of native ZC oil. It exhibited twenty times and twenty five times higher inhibitory activity against AChE and BChE, respectively. ZC oil loaded ME is an attractive formulation for further characterization and an in vivo study in an animal model with Alzheimer's disease.

Lessons Learned from the Crew Health Care System (CHeCS) Rack 1 Environmental Control and Life Support (ECLS) Design

Science.gov (United States)

Williams, David E.

2006-01-01

This paper will provide an overview of the International Space Station (ISS) Environmental Control and Life Support (ECLS) design of the Crew Health Care System (CHeCS) Rack 1 and it will document some of the lessons that have been learned to date for the ECLS equipment in this rack.

Substitution of the burning PRIOR SSB 10 for SSB7 in the Furnace 10 of the Company Major Ernesto Che Guevara

Directory of Open Access Journals (Sweden)

Ivett María Ramírez-Pérez

2017-01-01

Full Text Available One of the fundamental causes of massive destruction of chambers and vaults in the Furnace of Reduction at the Ernesto Che Guevara Factory is due to operate the combustion chambers with excess of contribution of heat, causing that the flame of very high temperature penetrates into the homes, affecting the throats of the chambers, the vaults, teeth and arms. The burners current are Prior SSB10. In this paper is demonstrated that the burning Prior SSB 10 have double productivity that the SSB 7 with the same quantity of air to the burner. It is evaluated the substitution of the burning Prior SSB 10 by SSB 7 on the operation of the Furnace of Reduction No. 10 at the Ernesto Che Guevara (ECG Factory. Demonstrating that the change not produce variations in the operation.

Cherenkov and scintillation light separation on the CheSS experiment

Science.gov (United States)

Caravaca, Javier; Land, Benjamin; Descamps, Freija; Orebi Gann, Gabriel D.

2016-09-01

Separation of the scintillation and Cherenkov light produced in liquid scintillators enables outstanding capabilities for future particle detectors, the most relevant being: particle directionality information in a low energy threshold detector and improved particle identification. The CheSS experiment uses an array of small, fast photomultipliers (PMTs) and state-of-the-art electronics to demonstrate the reconstruction of a Cherenkov ring in liquid scintillator using two techniques: based on the photon density and using the photon hit time information. A charged particle ionizing a scintillation medium produces a prompt Cherenkov cone and late isotropic scintillation light, typically delayed by several ns. The fast response of our PMTs and DAQ provides a precision well below the ns level, making possible the time separation. Furthermore, the usage of the new developed water-based liquid scintillators (WbLS) enhances the separation since it allows tuning of the Cherenkov/Scintillation ratio. Latest results on the separation for pure liquid scintillators and WbLS will be presented.

Toxicological Differences Between NMDA Receptor Antagonists and Cholinesterase Inhibitors.

Science.gov (United States)

Shi, Xiaodong; Lin, Xiaotian; Hu, Rui; Sun, Nan; Hao, Jingru; Gao, Can

2016-08-01

Cholinesterase inhibitors (ChEIs), represented by donepezil, rivastigmine, and galantamine, used to be the only approved class of drugs for the treatment of Alzheimer's disease. After the approval of memantine by the Food and Drug Administration (FDA), N-methyl-d-aspartic acid (NMDA) receptor antagonists have been recognized by authorities and broadly used in the treatment of Alzheimer's disease. Along with complementary mechanisms of action, NMDA antagonists and ChEIs differ not only in therapeutic effects but also in adverse reactions, which is an important consideration in clinical drug use. And the number of patients using NMDA antagonists and ChEIs concomitantly has increased, making the matter more complicated. Here we used the FDA Adverse Event Reporting System for statistical analysis , in order to compare the adverse events of memantine and ChEIs. In general, the clinical evidence confirmed the safety advantages of memantine over ChEIs, reiterating the precautions of clinical drug use and the future direction of antidementia drug development. © The Author(s) 2016.

Méthodes de levée de dormance de la noix de cola fraîche ( Cola ...

African Journals Online (AJOL)

Cette étude avait pour objectif de proposer une méthode efficace de germination de la noix de cola fraîche, en vue d'une réduction significative du délai de germination à travers un test comparatif de traitement de la noix par blessure, humidification et chaleur. Méthodologie et résultats: L'étude a été mise en place selon un ...

Development of HuperTacrines as non-toxic, cholinesterase inhibitors for the potential treatment of Alzheimer's disease.

Science.gov (United States)

Chioua, Mourad; Pérez, Marta; Bautista-Aguilera, Oscar M; Yañez, Matilde; López, Manuela G; Romero, Alejandro; Cacabelos, Ramón; de la Bellacasa, Raimon Puig; Brogi, Simone; Butini, Stefania; Borrell, José I; Marco-Contelles, Jose

2015-01-01

This paper describes our preliminary results on the ADMET, synthesis, biochemical evaluation, and molecular modeling of racemic HuperTacrines (HT), new hybrids resulting from the juxtaposition of huperzine A and tacrine for the potential treatment of Alzheimer's disease (AD). The synthesis of these HT was executed by Friedländer-type reactions of 2-amino-6-oxo-1,6-dihydropyridine-3-carbonitriles, or 7-amino-2-oxo-1,2,3,4-tetrahydro-1,6-naphthyridine- 8-carbonitriles, with cyclohexanone. In the biochemical evaluation, initial and particular attention was devoted to test their toxicity on human hepatoma cells, followed by the in vitro inhibition of human cholinesterases (hAChE, and hBuChE), and the kinetics/mechanism of the inhibition of the most potent HT; simultaneous molecular modeling on the best HT provided the key binding interactions with the human cholinesterases. >From these analyses, (±)-5-amino-3-methyl- 3,4,6,7,8,9-hexahydrobenzo[b][1,8]naphthyridin-2(1H)-one (HT1) and (±)-5-amino-3-(2,6-dichlorophenyl)-3,4,6,7,8,9- hexahydrobenzo[b][1,8]naphthyridin-2(1H)-one (HT3) have emerged as characterized by extremely low liver toxicity reversible mixed-type, selective hAChE and, quite selective irreversible hBuChEIs, respectively, showing also good druglike properties for AD-targeted drugs.

Molecular Cloning of Human Gene(s) Directing the Synthesis of Nervous System Cholinesterases

Science.gov (United States)

1987-09-01

responsible for at least some of the symptoms observed in hyperthyroidism . The location of primary sequences of human ChE showing high homology to bovine...verteLrates both classes exist in the heart. Humans having non- functional BuChE in the serum show no known symptoms of illness (15) and exhibit normal...become a "physiological nuisance" in cases of hyperthyroidism (such as Graves’ ophthalmopathy). In this disorder, there exists an overproduction of the

CheD: chemical database compilation tool, Internet server, and client for SQL servers.

Science.gov (United States)

Trepalin, S V; Yarkov, A V

2001-01-01

An efficient program, which runs on a personal computer, for the storage, retrieval, and processing of chemical information, is presented, The program can work both as a stand-alone application or in conjunction with a specifically written Web server application or with some standard SQL servers, e.g., Oracle, Interbase, and MS SQL. New types of data fields are introduced, e.g., arrays for spectral information storage, HTML and database links, and user-defined functions. CheD has an open architecture; thus, custom data types, controls, and services may be added. A WWW server application for chemical data retrieval features an easy and user-friendly installation on Windows NT or 95 platforms.

Possible mechanisms for sensitivity to organophosphorus and carbamate insecticides in eastern screech-owls and American kestrels

Science.gov (United States)

Vyas, N.B.; Thiele, L.A.; Garland, S.C.

1998-01-01

Effects of a single dietary exposure to fenthion and carbofuran on the survival, feeding behavior and brain ChE activity of eastern screech-owls, Otus asio and American kestrels, Falco sparverius, were evaluated. Birds were exposed to fenthion (23.6–189.0 ppm) or carbofuran (31.7–253.6 ppm) via meatballs. Carbofuran-exposed owls ate either ≤10% or ≥80% of the meatball whereas all kestrels ate ≤10% of the meatball before exhibiting acute signs of toxicity. Fenthion-exposed owls and kestrels displayed a wide spectrum of meatball consumption (<10–100%). Significant brain ChE inhibition was observed in dead and surviving kestrels exposed to fenthion and carbofuran and dead owls exposed to fenthion (P<0.0001). Brain ChE activity of owls exposed to carbofuran that survived was not different from that of controls (P=0.25). Data suggest: (1) slow feeding on a carbamate-contaminated item may provide limited protection from the toxicity of the chemical at certain rates of exposure; (2) the degree of ChE inhibition at neuromuscular junctions may be critical in determining the sensitivity of a species to a carbamate insecticide; (3) sensitivity may be a function of the ChE affinity for the carbamate inhibitor; and (4) the importance of neuromuscular junction ChE depression in determining the sensitivity of an animal may be species-specific.

Possible mechanisms for sensitivity to organophosphorus and carbamate insecticides in eastern screech-owls and American kestrels.

Science.gov (United States)

Vyas, N B; Thiele, L A; Garland, S C

1998-07-01

Effects of a single dietary exposure to fenthion and carbofuran on the survival, feeding behavior and brain ChE activity of eastern screech-owls, Otus asio and American kestrels, Falco sparverius, were evaluated. Birds were exposed to fenthion (23.6-189.0 ppm) or carbofuran (31.7-253.6 ppm) via meatballs. Carbofuran-exposed owls ate either or = 80% of the meatball whereas all kestrels ate meatball before exhibiting acute signs of toxicity. Fenthion-exposed owls and kestrels displayed a wide spectrum of meatball consumption (< 10-100%). Significant brain ChE inhibition was observed in dead and surviving kestrels exposed to fenthion and carbofuran and dead owls exposed to fenthion (P < 0.0001). Brain ChE activity of owls exposed to carbofuran that survived was not different from that of controls (P = 0.25). Data suggest: (1) slow feeding on a carbamate-contaminated item may provide limited protection from the toxicity of the chemical at certain rates of exposure; (2) the degree of ChE inhibition at neuromuscular junctions may be critical in determining the sensitivity of a species to a carbamate insecticide; (3) sensitivity may be a function of the ChE affinity for the carbamate inhibitor; and (4) the importance of neuromuscular junction ChE depression in determining the sensitivity of an animal may be species-specific.

Acetylcholine muscarinic receptors and response to anti-cholinesterase therapy in patients with Alzheimer's disease

International Nuclear Information System (INIS)

Brown, Derek; Chisholm, Jennifer A.; Patterson, Jim; Wyper, David; Owens, Jonathan; Pimlott, Sally

2003-01-01

An acetylcholine deficit remains the most consistent neurotransmitter abnormality found in Alzheimer's disease and various therapeutic agents have been targeted at this. In this study we investigated the action of Donepezil, a cholinesterase inhibitor that has few side-effects. In particular we set out to investigate whether muscarinic acetylcholine receptor (mAChR) availability influences the response to this therapy. We used the novel single-photon emission tomography (SPET) tracer (R,R)[ 123 I]I-quinuclidinyl benzilate (R,R[ 123 I]I-QNB), which has high affinity for the M1 subtype of mAChR. Regional cerebral perfusion was also assessed using technetium-99m hexamethylpropylene amine oxime. We investigated 20 patients on Donepezil treatment and ten age-matched controls. The results showed a reduction in (R,R)[ 123 I]I-QNB binding in the caudal anterior cingulate in patients compared with controls and relatively high binding in the putamen and rostral anterior cingulate, suggesting a relative sparing of mAChR in these regions. The main finding of the study was that mAChR availability as assessed by (R,R)[ 123 I]I-QNB binding did not distinguish responders from non-responders. Interestingly, we found that the extent of cognitive improvement showed no positive correlation with (R,R)[ 123 I]I-QNB binding in any brain region but was inversely related to binding in the insular cortex. This suggests that, within the advised cognitive performance band for use of Donepezil, response is greater in those patients with evidence of a more marked cholinergic deficit. A larger study should investigate this. (orig.)

Risk Factors for Nursing Home Placement in Alzheimer's Disease: A Longitudinal Study of Cognition, ADL, Service Utilization, and Cholinesterase Inhibitor Treatment

Science.gov (United States)

Wattmo, Carina; Wallin, Asa K.; Londos, Elisabet; Minthon, Lennart

2011-01-01

Purpose of the Study: To identify risk factors for early nursing home placement (NHP) in Alzheimer's disease (AD), focusing on the impact of longitudinal change in cognition, activities of daily living (ADL), service utilization, and cholinesterase inhibitor treatment (ChEI). Design and Methods: In an open, 3-year, prospective, multicenter study…

Cholinesterases: structure of the active site and mechanism of the effect of cholinergic receptor blockers on the rate of interaction with ligands

Energy Technology Data Exchange (ETDEWEB)

Antokhin, A M; Gainullina, E T; Taranchenko, V F [Federal State Agency ' 27 Scientific Centre of Ministry of Defence of the Russian Federation' (Russian Federation); Ryzhikov, S B; Yavaeva, D K [Department of Physics, M.V.Lomonosov Moscow State University (Russian Federation)

2010-10-19

Modern views on the structure of cholinesterase active sites and the mechanism of their interaction with organophosphorus inhibitors are considered. The attention is focused on the mechanism of the effect of cholinergic receptor blockers, acetylcholine antagonists, on the rate of interaction of acetylcholine esterase with organophosphorus inhibitors.

Cholinesterases: structure of the active site and mechanism of the effect of cholinergic receptor blockers on the rate of interaction with ligands

International Nuclear Information System (INIS)

Antokhin, A M; Gainullina, E T; Taranchenko, V F; Ryzhikov, S B; Yavaeva, D K

2010-01-01

Modern views on the structure of cholinesterase active sites and the mechanism of their interaction with organophosphorus inhibitors are considered. The attention is focused on the mechanism of the effect of cholinergic receptor blockers, acetylcholine antagonists, on the rate of interaction of acetylcholine esterase with organophosphorus inhibitors.

Effect of in vivo nicotine exposure on chlorpyrifos pharmacokinetics and pharmacodynamics in rats

Energy Technology Data Exchange (ETDEWEB)

Lee, Soo Kwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

2010-03-30

Chlorpyrifos (CPF) is one of the most studied and widely used broad spectrum organophosphorus (OP) insecticides. The neurotoxicity of CPF results from inhibition of cholinesterase (ChE) by its metabolite, chlorpyrifos-oxon (CPF-oxon), which subsequently leads to cholinergic hyperstimulation. The routine consumption of alcoholic beverages and tobacco products will modify a number of metabolic and physiological processes which may impact the metabolism and pharmacokinetics of other xenobiotics including pesticides. The objective of this study was to evaluate the influence of repeated ethanol and nicotine co-exposure on in vivo CPF pharmacokinetics and pharmacodynamics. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine along with changes in plasma and brain AChE activities were measured in male Sprague-Dawley (S-D) rats. Animals were repeatedly treated with either saline or ethanol (1 g/kg/day, po) and nicotine (1 mg/kg/day, sc) in addition to CPF (1 or 5 mg/kg/day, po) for 7 days. Rats were sacrificed at times from 1 to 24 hr post-last dosing of CPF. There were apparent differences in blood TCPy pharmacokinetics following ethanol and nicotine pretreatments in both CPF dose groups, which showed higher TCPy peak concentrations and increased blood TCPy AUC in ethanol and nicotine groups over CPF-only (~1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain acetylcholinesterase (AChE) activities from both ethanol and nicotine-treated groups showed substantially less inhibition following repeated 5 mg CPF/kg dosing compared to CPF-only controls (96 ± 13 and 66 ± 7% of naïve at 4 hr post-last CPF dosing, respectively). Inhibition of brain AChE activities was minimal in both 1 mg CPF/kg/day dosing groups, but a similar trend indicating less inhibition following ethanol/nicotine pretreatment was apparent. No differences were observed in plasma ChE activities due to the combined alcohol and nicotine treatments. In vitro, CPF

A 36,000-Year-Old Volcanic Eruption Depicted in the Chauvet-Pont d'Arc Cave (Ardèche, France)?

Science.gov (United States)

Nomade, Sébastien; Genty, Dominique; Sasco, Romain; Scao, Vincent; Féruglio, Valérie; Baffier, Dominique; Guillou, Hervé; Bourdier, Camille; Valladas, Hélène; Reigner, Edouard; Debard, Evelyne; Pastre, Jean-François; Geneste, Jean-Michel

2016-01-01

Among the paintings and engravings found in the Chauvet-Pont d'Arc cave (Ardèche, France), several peculiar spray-shape signs have been previously described in the Megaloceros Gallery. Here we document the occurrence of strombolian volcanic activity located 35 km northwest of the cave, and visible from the hills above the cave entrance. The volcanic eruptions were dated, using 40Ar/39Ar, between 29 ± 10 ka and 35 ± 8 ka (2σ), which overlaps with the 14C AMS and thermoluminescence ages of the first Aurignacian occupations of the cave in the Megaloceros Gallery. Our work provides the first evidence of an intense volcanic activity between 40 and 30 ka in the Bas-Vivarais region, and it is very likely that Humans living in the Ardèche river area witnessed one or several eruptions. We propose that the spray-shape signs found in the Chauvet-Pont d'Arc cave could be the oldest known depiction of a volcanic eruption, predating by more than 34 ka the description by Pliny the Younger of the Vesuvius eruption (AD 79) and by 28 ka the Çatalhöyük mural discovered in central Turkey.

Diethyl 2-(Phenylcarbamoylphenyl Phosphorothioates: Synthesis, Antimycobacterial Activity and Cholinesterase Inhibition

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Jarmila Vinšová

2014-05-01

Full Text Available A new series of 27 diethyl 2-(phenylcarbamoylphenyl phosphorothioates (thiophosphates was synthesized, characterized by NMR, IR and CHN analyses and evaluated against Mycobacterium tuberculosis H37Rv, Mycobacterium avium and two strains of Mycobacterium kansasii. The best activity against M. tuberculosis was found for O-{4-bromo-2-[(3,4-dichlorophenylcarbamoyl]phenyl} O,O-diethyl phosphorothioate (minimum inhibitory concentration of 4 µM. The highest activity against nontuberculous mycobacteria was exhibited by O-(5-chloro-2-{[4-(trifluoromethylphenyl]carbamoyl}-phenyl O,O-diethyl phosphorothioate with MIC values from 16 µM. Prepared thiophosphates were also evaluated against acetylcholinesterase from electric eel and butyrylcholinesterase from equine serum. Their inhibitory activity was compared to that of the known cholinesterases inhibitors galanthamine and rivastigmine. All tested compounds showed a higher (for AChE inhibition and comparable (for BChE inhibition activity to that of rivastigmine, with IC50s within the 8.04 to 20.2 µM range.

Molecular basis of neural function

International Nuclear Information System (INIS)

Tucek, S.; Stipek, S.; Stastny, F.; Krivanek, J.

1986-01-01

The conference proceedings contain abstracts of plenary lectures, of young neurochemists' ESN honorary lectures, lectures at symposia and workshops and poster communications. Twenty abstracts were inputted in INIS. The subject of these were the use of autoradiography for the determination of receptors, cholecystokinin, nicotine, adrenaline, glutamate, aspartate, tranquilizers, for distribution and pharmacokinetics of obidoxime-chloride, for cell proliferation, mitosis of brain cells, DNA repair; radioimmunoassay of cholinesterase, tyrosinase; positron computed tomography of the brain; biological radiation effects on cholinesterase activity; tracer techniques for determination of adrenaline; and studies of the biological repair of nerves. (J.P.)

Fractional derivatives. An introduction; Derivate frazionarie. Che cosa sono, a cosa servono

Energy Technology Data Exchange (ETDEWEB)

Dattoli, G. [ENEA, Div. Fisica Applicata, Centro Ricerche Frascati, Rome (Italy)

2001-07-01

In this item is presented a brief survey of fractional calculus and of the relevant applications. In the work are discussed different points of view of the operation of fractional derivative and present a unifying definition. The role played by fractional derivatives and integrals within the framework of integral transform is analyzed. [Italian] In questo articolo si traccia un profilo del cosidetto calcolo frazionario e delle relative applicazioni a problemi di matematica pura ed applicata. Si discutono varie definizioni dell'operazione di derivata frazionaria, non tutte coincidenti fra loro, e si mostra come sia possibile proporre una definizione univoca che inglobi tutte le altre. Si analizza infine il ruolo giocato dalle derivate e dagli integrali frazionari e, piu' in generale, quello degli operatori differenziali ad esponente frazionario, nell'ambito della teoria delle rappresentazioni integrali.

Impact of cholinesterase inhibitors on behavioral and psychological symptoms of Alzheimer’s disease: A meta-analysis

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Noll Campbell

2008-12-01

Full Text Available Noll Campbell1, Amir Ayub2, Malaz A Boustani2, Chris Fox3, Martin Farlow4, Ian Maidment3, Robert Howard51Wishard Health Services, Indianapolis, Indiana; 2Indiana University Center for Aging Research, Regenstrief Institute, Inc., Indianapolis, Indiana; 3University of Kent, Kent, United Kingdom; 4Indiana University School of Medicine, Indianapolis, Indiana; 5King’s College, London, United KingdomObjective: To determine the efficacy of cholinesterase inhibitors (ChEIs in improving the behavioral and psychological symptoms of dementia (BPSD in patients with Alzheimer’s disease (AD.Data sources: We searched MEDLINE, Cochrane Registry, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL from 1966 to 2007. We limited our search to English Language, full text, published articles and human studies.Data extraction: We included randomized, double-blind, placebo-controlled trials evaluating the efficacy of donepezil, rivastigmine, or galantamine in managing BPSD displayed by AD patients. Using the United States Preventive Services Task Force (USPSTF guidelines, we critically appraised all studies and included only those with an attrition rate of less than 40%, concealed measurement of the outcomes, and intention to treat analysis of the collected data. All data were imputed into pre-defined evidence based tables and were pooled using the Review Manager 4.2.1 software for data synthesis.Results: We found 12 studies that met our inclusion criteria but only nine of them provided sufficient data for the meta-analysis. Among patients with mild to severe AD and in comparison to placebo, ChEIs as a class had a beneficial effects on reducing BPSD with a standard mean difference (SMD of −0.10 (95% confidence interval [CI]; −0.18, −0.01 and a weighted mean difference (WMD of −1.38 neuropsychiatry inventory point (95% CI; −2.30, −0.46. In studies with mild AD patients, the WMD was −1.92 (95% CI; −3.18, −0.66; and in studies

Piper betle leaves: profiling phenolic compounds by HPLC/DAD-ESI/MS(n) and anti-cholinesterase activity.

Science.gov (United States)

Ferreres, Federico; Oliveira, Andreia P; Gil-Izquierdo, Angel; Valentão, Patrícia; Andrade, Paula B

2014-01-01

Piper betle L. is a widely distributed plant in the tropical and subtropical regions, its leaves being largely consumed as a masticator and mouth freshener. The purposes of this work were to characterise the phenolic profile of this species and to improve knowledge of its anti-cholinesterase properties. The phenolic composition of P. betle leaf aqueous and ethanol extracts was characterised by HPLC coupled with a diode-array detector and combined with electrospray ionisation tandem MS, and in vitro cholinesterase inhibitory capacity of both extracts was assessed by spectrophotometric microassays. The effect on neuronal cells (SH-SY5Y) viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction and lactate dehydrogenase leakage. Twelve phenolic compounds, comprising a phenylpropanoid, five cinnamoyl and six flavonoids derivatives were identified in P. betle leaves. Hydroxychavicol was the major compound in both extracts; however, the aqueous extract presented a greater diversity of compounds. Both extracts showed strong activity against both acetyl- and butyrylcholinesterase, which can be due, at least partially, to the phenolic composition. Furthermore, the aqueous extract proved to be cytotoxic to human neuroblastoma cells at concentrations higher than 500 µg/mL. The results suggest that the consumption of P. betle leaves as an infusion can have a positive impact in the prevention and treatment of neurodegenerative diseases. Apigenin and luteolin derivatives are reported for the first time in this species. Copyright © 2014 John Wiley & Sons, Ltd.

Analysis of Amaryllidaceae alkaloids from Zephyranthes grandiflora by GC/MS and their cholinesterase activity

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Lucie Cahlíková

2011-05-01

Full Text Available Amaryllidaceae are known as ornamental plants, furthermore some species of this family contain galanthamine, an acetylcholinesterase inhibitor approved for the treatment of Alzheimer's disease, and other alkaloids with interesting pharmacological activity. The chemical composition of alkaloids from Zephyranthes grandiflora Lindl. was analyzed by GC/MS. Seven known compounds, belonging to five structural types of Amaryllidaceae alkaloids, were identified. The alkaloid extract from the bulbs showed promising cholinesterase inhibitory activities against human blood acetylcholinesterase (HuAChE; IC50 39.2±3.0 µg/mL and human plasma butyrylcholinesterase (HuBuChE; IC50 356±9.3 µg/mL.

Analysis of Amaryllidaceae alkaloids from Zephyranthes grandiflora by GC/MS and their cholinesterase activity

Directory of Open Access Journals (Sweden)

Lucie Cahlíková

2011-08-01

Full Text Available Amaryllidaceae are known as ornamental plants, furthermore some species of this family contain galanthamine, an acetylcholinesterase inhibitor approved for the treatment of Alzheimer's disease, and other alkaloids with interesting pharmacological activity. The chemical composition of alkaloids from Zephyranthes grandiflora Lindl. was analyzed by GC/MS. Seven known compounds, belonging to five structural types of Amaryllidaceae alkaloids, were identified. The alkaloid extract from the bulbs showed promising cholinesterase inhibitory activities against human blood acetylcholinesterase (HuAChE; IC50 39.2±3.0 µg/mL and human plasma butyrylcholinesterase (HuBuChE; IC50 356±9.3 µg/mL.

Development of organophosphate hydrolase activity in a bacterial homolog of human cholinesterase

Science.gov (United States)

Legler, Patricia; Boisvert, Susanne; Compton, Jaimee; Millard, Charles

2014-07-01

We applied a combination of rational design and directed evolution (DE) to Bacillus subtilis p-nitrobenzyl esterase (pNBE) with the goal of enhancing organophosphorus acid anhydride hydrolase (OPAAH) activity. DE started with a designed variant, pNBE A107H, carrying a histidine homologous with human butyrylcholinesterase G117H to find complementary mutations that further enhance its OPAAH activity. Five sites were selected (G105, G106, A107, A190, and A400) within a 6.7 Å radius of the nucleophilic serine O?. All 95 variants were screened for esterase activity with a set of five substrates: pNP-acetate, pNP-butyrate, acetylthiocholine, butyrylthiocholine, or benzoylthiocholine. A microscale assay for OPAAH activity was developed for screening DE libraries. Reductions in esterase activity were generally concomitant with enhancements in OPAAH activity. One variant, A107K, showed an unexpected 7-fold increase in its kcat/Km for benzoylthiocholine, demonstrating that it is also possible to enhance the cholinesterase activity of pNBE. Moreover, DE resulted in at least three variants with modestly enhanced OPAAH activity compared to wild type pNBE. A107H/A190C showed a 50-fold increase in paraoxonase activity and underwent a slow time- and temperature-dependent change affecting the hydrolysis of OPAA and ester substrates. Structural analysis suggests that pNBE may represent a precursor leading to human cholinesterase and carboxylesterase 1 through extension of two vestigial specificity loops; a preliminary attempt to transfer the Ω-loop of BChE into pNBE is described. pNBE was tested as a surrogate scaffold for mammalian esterases. Unlike butyrylcholinesterase and pNBE, introducing a G143H mutation (equivalent to G117H) did not confer detectable OP hydrolase activity on human carboxylesterase 1. We discuss the importance of the oxyanion-hole residues for enhancing the OPAAH activity of selected serine hydrolases.

Cholinesterase activity in the cup oyster Saccostrea sp. exposed to chlorpyrifos, imidacloprid, cadmium and copper.

Science.gov (United States)

Moncaleano-Niño, Angela M; Luna-Acosta, Andrea; Gómez-Cubillos, Maria Camila; Villamil, Luisa; Ahrens, Michael J

2018-04-30

In the present study, the sensitivity and concentration dependence of three functionally-defined components of cholinesterase activity (total: T-ChE; eserine-sensitive: Es-ChE; and eserine-resistant: Er-ChE) were quantified in the gill, digestive gland and adductor muscle of the tropical cup oyster Saccostrea sp., following acute (96h) aqueous exposure to commercial formulations of the organophosphate (OP) insecticide chlorpyrifos and the neonicotinoid (NN) imidacloprid (concentration range: 0.1-100mg/L), as well as to dissolved cadmium and copper (concentration range: 1-1000μg/L). Oysters (1.5-5.0cm shell length), field-collected from a boating marina in Santa Marta, Colombia (Caribbean Sea) were exposed in the laboratory to each substance at five concentrations. T-ChE, Es-ChE, and Er-ChE activity were quantified in the three tissues in pools of 5 individuals (3 replicates per concentration), before and after inhibition with the total cholinesterase inhibitor eserine (physostigmine, 100µM). Oysters exposed to chlorpyrifos, imidacloprid and Cd showed reduced T-ChE and Es-ChE activity in gills at highest exposure concentrations, with Es-ChE activity being inhibited proportionally more so than T-ChE, whereas Er-ChE activity showed no significant concentration-response. Digestive gland also showed diminished T-ChE, Es-ChE and Er-ChE activity for highest chlorpyrifos and Cd concentrations relative to controls, but an increase of T-ChE and Er-ChE activity at the highest imidacloprid concentration (100mg/L). For Cu, T-ChE, Es-ChE and Er-ChE activities in gills and digestive gland were elevated relative to controls in oysters exposed to Cu concentrations > 100µg/L. In adductor muscle, T-ChE, Es-ChE and Er-ChE activity showed no apparent pattern for any of the four xenobiotics and concentration levels tested. Although this study confirms acute (96h) concentration-dependent reduction of tissue T-ChE and Es-ChE activity in gills and digestive glands of Saccostrea sp

Antioxidant activity and cholinesterase inhibition studies of four flavouring herbs from Alentejo.

Science.gov (United States)

Arantes, Sílvia; Piçarra, Andreia; Candeias, Fátima; Caldeira, A Teresa; Martins, M Rosário; Teixeira, Dora

2017-09-01

Essential oils (EOs) and aqueous extracts of aerial parts of four aromatic species, Calamintha nepeta, Foeniculum vulgare, Mentha spicata and Thymus mastichina, from southwest of Portugal were characterised chemically and analysed in order to evaluate their antioxidant potential and cholinesterase inhibitory activities. The main components of EOs were oxygenated monoterpenes, and aqueous extracts were rich in phenol and flavonoid compounds. EOs and aqueous extracts presented a high antioxidant potential, with ability to protect the lipid substrate, free radical scavenging and iron reducing power. Furthermore, EOs and extracts showed AChE and BChE inhibitory activities higher than rivastigmine, the standard drug. Results suggested the potential use of EOs and aqueous extracts of these flavouring herbs as nutraceutical or pharmaceutical preparations to minimise the oxidative stress and the progression of degenerative diseases.

14C-labeling of a tetrahydroacridine, a novel CNS-selective cholinesterase inhibitor

International Nuclear Information System (INIS)

Nishioka, Kazuhiko; Kamada, Takeshi; Kanamaru, Hiroshi

1992-01-01

9-Amino-8-fluoro-2,4-methano-1,2,3,4-tetrahydroacridine citrate (SM-10888), a novel cholinesterase inhibitor, was labeled with carbon-14 at C9 of the tetrahydroacridine ring for use in metabolic studies. Carbonation of 2,6-difluorophenyllithium (3) with [ 14 C]carbon dioxide gave the acid (4). Chlorination of 4 followed by treatment of the resulting acid chloride with ammonia afforded the amide (5). Dehydration of 5 with thionyl chloride and subsequent displacement reaction with ammonia gave the aminobenzonitrile (7). Condensation of 7 with the ketone (8) in the presence of anhydrous zinc chloride yielded the aminoacridine (9), which was treated with citric acid to afford [9- 14 C]SM-10888 (1). The overall yield of 1 was 37% from 2, and the specific activity was 1.35 GBq/mmol. (author)

Cholinesterase response in the rhabdomyosarcoma tumor and small intestine of the BALB/c mice and the radioprotective actions of exogenous ATP after lethal dose of neutron radiation

International Nuclear Information System (INIS)

Szeinfeld, D.; De Villiers, N.

1993-01-01

The rhabdomyosarcoma tumors were subjected to different doses of 2.0, 3.8 and 7.0 Gy from a neutron beam facility p(66 MeV)/Be. Elevated levels of cholinesterase activity are observed in which there is a correlation between the different doses of neutron radiation and the augmentation response of this enzyme. The increase of cholinesterase activity after 7 Gy neutron irradiation as a feature of involvement in the homeostatic mechanism maintaining the proper choline/acetylcholine ratio in the cell is also observed at 1 and 24 h in both tissues, rhabdomyosarcoma and small intestine. The activity of the enzyme after neutron irradiation with prior administration of ATP showed smaller increases when compared with increase observed after neutron irradiation alone. Moreover in the present work the protective mechanism of ATP in the response of cholinesterase activity is marked differential between both, normal and tumoral tissue and correlated inversely with the administered of the following concentrations of exogenous ATP (8, 25, 80, 250, and 700 mg/kg body weight) prior to exposure to 7 Gy neutron radiation. These results reflect the radioprotective ability of exogenous ATP to exert a number of metabolic adaptations as a defense mechanism in which the cell exposed to neutron radiation could remain viable because the injury is potentially repairable. (orig.) [de

Tritium labeling of a powerful methylphosphonate inhibitor of cholinesterase: synthesis and biological applications

International Nuclear Information System (INIS)

Balan, A.; Barness, I.; Simon, G.; Levy, D.; Ashani, Y.

1988-01-01

7-(Methylethoxy phosphinyloxy)-1-methyl-quinolinium iodide (MEPQ), a powerful anti-cholinesterase methylphosphonate ester, was labeled with tritium (9 Ci/mmol) at the methylphosphonyl moiety (TCH2P(O)(OR)X) by an iodine-tritium replacement reaction. Kinetic measurements of the rate of inhibition of acetylcholinesterase (AChE) by [ 3 H]MEPQ and its rate of hydrolysis in alkaline solution confirmed the identity of [ 3 H]MEPQ with authentic MEPQ, which was prepared by the same reaction sequences. Gel-filtration experiments verified the radiospecificity of [ 3 H]MEPQ. In vitro radiolabeling of both AChE and butyrylcholinesterase along with the whole-body autoradiography of [ 3 H]MEPQ-treated mice suggests that [ 3 H]MEPQ is a convenient marker for studying biological systems containing these esterases

Synthesis, characterization, X-ray crystallography, acetyl cholinesterase inhibition and antioxidant activities of some novel ketone derivatives of gallic hydrazide-derived Schiff bases.

Science.gov (United States)

Gwaram, Nura Suleiman; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen; Buckle, Michael J C; Sukumaran, Sri Devi; Chung, Lip Yong; Othman, Rozana; Alhadi, Abeer A; Yehye, Wageeh A; Hadi, A Hamid A; Hassandarvish, Pouya; Khaledi, Hamid; Abdelwahab, Siddig Ibrahim

2012-02-28

Alzheimer's disease (AD) is the most common form of dementia among older people and the pathogenesis of this disease is associated with oxidative stress. Acetylcholinesterase inhibitors with antioxidant activities are considered potential treatments for AD. Some novel ketone derivatives of gallic hydrazide-derived Schiff bases were synthesized and examined for their antioxidant activities and in vitro and in silico acetyl cholinesterase inhibition. The compounds were characterized using spectroscopy and X-ray crystallography. The ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays revealed that all the compounds have strong antioxidant activities. N-(1-(5-bromo-2-hydroxyphenyl)-ethylidene)-3,4,5-trihydroxybenzohydrazide (2) was the most potent inhibitor of human acetyl cholinesterase, giving an inhibition rate of 77% at 100 μM. Molecular docking simulation of the ligand-enzyme complex suggested that the ligand may be positioned in the enzyme's active-site gorge, interacting with residues in the peripheral anionic subsite (PAS) and acyl binding pocket (ABP). The current work warrants further preclinical studies to assess the potential for these novel compounds for the treatment of AD.

The Drosophila gene CheB42a is a novel modifier of Deg/ENaC channel function.

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Yehuda Ben-Shahar

2010-02-01

Full Text Available Degenerin/epithelial Na(+ channels (DEG/ENaC represent a diverse family of voltage-insensitive cation channels whose functions include Na(+ transport across epithelia, mechanosensation, nociception, salt sensing, modification of neurotransmission, and detecting the neurotransmitter FMRFamide. We previously showed that the Drosophila melanogaster Deg/ENaC gene lounge lizard (llz is co-transcribed in an operon-like locus with another gene of unknown function, CheB42a. Because operons often encode proteins in the same biochemical or physiological pathway, we hypothesized that CHEB42A and LLZ might function together. Consistent with this hypothesis, we found both genes expressed in cells previously implicated in sensory functions during male courtship. Furthermore, when coexpressed, LLZ coprecipitated with CHEB42A, suggesting that the two proteins form a complex. Although LLZ expressed either alone or with CHEB42A did not generate ion channel currents, CHEB42A increased current amplitude of another DEG/ENaC protein whose ligand (protons is known, acid-sensing ion channel 1a (ASIC1a. We also found that CHEB42A was cleaved to generate a secreted protein, suggesting that CHEB42A may play an important role in the extracellular space. These data suggest that CHEB42A is a modulatory subunit for sensory-related Deg/ENaC signaling. These results are consistent with operon-like transcription of CheB42a and llz and explain the similar contributions of these genes to courtship behavior.

Environmental contaminants in Texas, USA, wetland reptiles: Evaluation using blood samples

Science.gov (United States)

Clark, D.R.; Bickham, J.W.; Baker, D.L.; Cowman, D.F.

2000-01-01

Four species of reptiles (diamondback water snake [Nerodia rhombifer], blotched water snake [N. erythrogaster], cottonmouth [Agkistrodon piscivorus], and red-eared slider [Trachemys scripta]) were collected at two contaminated and three reference sites in Texas, USA. Old River Slough has received intensive applications of agricultural chemicals since the 1950s. Municipal Lake received industrial arsenic wastes continuously from 1940 to 1993. Blood samples were analyzed for organochlorines, potentially toxic elements, genetic damage, and plasma cholinesterase (ChE). Dichlorodiphenyldichloroethylene (DDE) concentrations reached as high as 3.0 ppm (wet weight) in whole blood of a diamondback water snake at Old River Slough, a level probably roughly equivalent to the maximum concentration found in plasma of peregrine falcons (Falco peregrinus) in 1978 to 1979 when DDE peaked in this sensitive species. Possible impacts on diamondback water snakes are unknown, but at least one diamondback water snake was gravid when captured, indicating active reproduction. Arsenic was not found in red-eared sliders (only species sampled) from Municipal Lake. Red-eared sliders of both sexes at Old River Slough showed declining levels of ChE with increasing mass, suggesting a life-long decrease of ChE levels. Possible negative population consequences are unknown, but no evidence was found in body condition (mass relative to carapace length) that red-eared sliders at either contaminated site were harmed.

A 36,000-Year-Old Volcanic Eruption Depicted in the Chauvet-Pont d’Arc Cave (Ardèche, France)?

Science.gov (United States)

Nomade, Sébastien; Genty, Dominique; Sasco, Romain; Scao, Vincent; Féruglio, Valérie; Baffier, Dominique; Guillou, Hervé; Bourdier, Camille; Valladas, Hélène; Reigner, Edouard; Debard, Evelyne; Pastre, Jean–François; Geneste, Jean-Michel

2016-01-01

Among the paintings and engravings found in the Chauvet-Pont d’Arc cave (Ardèche, France), several peculiar spray-shape signs have been previously described in the Megaloceros Gallery. Here we document the occurrence of strombolian volcanic activity located 35 km northwest of the cave, and visible from the hills above the cave entrance. The volcanic eruptions were dated, using 40Ar/39Ar, between 29 ± 10 ka and 35 ± 8 ka (2σ), which overlaps with the 14C AMS and thermoluminescence ages of the first Aurignacian occupations of the cave in the Megaloceros Gallery. Our work provides the first evidence of an intense volcanic activity between 40 and 30 ka in the Bas-Vivarais region, and it is very likely that Humans living in the Ardèche river area witnessed one or several eruptions. We propose that the spray-shape signs found in the Chauvet-Pont d’Arc cave could be the oldest known depiction of a volcanic eruption, predating by more than 34 ka the description by Pliny the Younger of the Vesuvius eruption (AD 79) and by 28 ka the Çatalhöyük mural discovered in central Turkey. PMID:26745626

Correlation interrelation between level of catecholamines and indices of cholinesterase system at minor radiation dose influence on liquidators of the Chernobyl NPP

International Nuclear Information System (INIS)

Makashev, Zh.K.; Zhurnist, A.G.; Uteshev, A.G.; Abylaev, Zh.A.

2004-01-01

For assessment of functional condition of sympathoadrenal system adrenalin (A) and noradrenaline (NA) concentrations were investigated as well as NA/A ratio in day's urine of Chernobyl NPP liquidators. Concurrently, it was determined the contents of acetylcholine and activity of cholinesterase in the blood serum of persons exposed to minor radiation dose with calculation of correlation Pearson coefficient. (author)

Occupational determinants of serum cholinesterase inhibition among organophosphate-exposed agricultural pesticide handlers in Washington State

Science.gov (United States)

Hofmann, Jonathan N; Keifer, Matthew C; De Roos, Anneclaire J; Fenske, Richard A; Furlong, Clement E; van Belle, Gerald; Checkoway, Harvey

2010-01-01

Objective To identify potential risk factors for serum cholinesterase (BuChE) inhibition among agricultural pesticide handlers exposed to organophosphate (OP) and N-methyl-carbamate (CB) insecticides. Methods We conducted a longitudinal study among 154 agricultural pesticide handlers who participated in the Washington State cholinesterase monitoring program in 2006 and 2007. BuChE inhibition was analyzed in relation to reported exposures before and after adjustment for potential confounders using linear regression. Odds ratios estimating the risk of ‘BuChE depression’ (>20% from baseline) were also calculated for selected exposures based on unconditional logistic regression analyses. Results An overall decrease in mean BuChE activity was observed among study participants at the time of follow-up testing during the OP/CB spray season relative to pre-season baseline levels (mean decrease of 5.6%, P < 0.001). Score for estimated cumulative exposure to OP/CB insecticides in the past 30 days was a significant predictor of BuChE inhibition (β = −1.74, P < 0.001). Several specific work practices and workplace conditions were associated with greater BuChE inhibition, including mixing/loading pesticides and cleaning spray equipment. Factors that were protective against BuChE inhibition included full-face respirator use, wearing chemical-resistant boots, and storing personal protective equipment in a locker at work. Conclusions Despite existing regulations, agricultural pesticide handlers continue to be exposed to OP/CB insecticides at levels resulting in BuChE inhibition. These findings suggest that modifying certain work practices could potentially reduce BuChE inhibition. Replication from other studies will be valuable. PMID:19819864

Preparation and in vitro screening of symmetrical bis-isoquinolinium cholinesterase inhibitors bearing various connecting linkage--implications for early Myasthenia gravis treatment.

Science.gov (United States)

Musilek, Kamil; Komloova, Marketa; Holas, Ondrej; Hrabinova, Martina; Pohanka, Miroslav; Dohnal, Vlastimil; Nachon, Florian; Dolezal, Martin; Kuca, Kamil

2011-02-01

Inhibitors of acetylcholinesterase are compounds widely used in the treatment of various diseases, such as Alzheimer's disease, glaucoma and Myasthenia gravis (MG). Compounds used in the therapy of MG posses a positive charge in the molecule to ensure peripheral effect of action and minimal blood-brain barrier penetration. The most prescribed carbamate inhibitors are however known for many severe side effects related to the carbamylation of AChE. This paper describes preparation and in vitro evaluation of 20 newly prepared bis-isoquinolinium inhibitors of potential concern for MG. The newly prepared compounds were evaluated in vitro on human recombinant AChE and human plasmatic butyrylcholinesterase (BChE). Their inhibitory ability was expressed as IC50 and compared to chosen standards ambenonium dichloride, edrophonium chloride, BW284c51 and ethopropazine hydrochloride. Three novel compounds presented promising inhibition (in nM range) of both enzymes in vitro better or similar to edrophonium and BW284c51, but worse to ambenonium. The novel inhibitors did not present higher selectivity toward AChE or BChE. The kinetic assay confirmed non-competitive inhibition of hAChE by two selected promising novel compounds. Two newly prepared compounds were also chosen for docking studies that confirmed apparent π-π or π-cationic interactions aside the cholinesterases catalytic sites. The SAR findings were discussed. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Effect of In Vivo Nicotine Exposure on Chlorpyrifos Pharmacokinetics and Pharmacodynamics in Rats

Energy Technology Data Exchange (ETDEWEB)

Lee, Sookwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

2010-03-30

Routine use of tobacco products may modify physiological and metabolic functions, including drug metabolizing enzymes, which may impact the pharmacokinetics of environmental contaminants. Chlorpyrifos is an organophosphorus (OP) insecticide that is bioactivated to chlorpyrifos-oxon, and manifests its neurotoxicity by inhibiting acetylcholinesterase (AChE). The objective of this study was to evaluate the impact of repeated nicotine exposure on the pharmacokinetics of chlorpyrifos (CPF) and its major metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine and also to determine the impact on cholinesterase (ChE) activity in plasma and brain. Animals were exposed to 7-daily doses of either 1 mg nicotine/kg or saline (sc), and to either a single oral dose of 35 mg CPF/kg or a repeated dose of 5 mg CPF/kg/day for 7 days. Groups of rats were then sacrificed at multiple time-points after receiving the last dose of CPF. Repeated nicotine and CPF exposures resulted in enhanced metabolism of CPF to TCPy, as evidenced by increases in the measured TCPy concentration and AUC in blood. However, there was no significant difference in the amount of TCPy (free or total) excreted in the urine. The extent of brain acetylcholinesterase (AChE) inhibition was reduced due to nicotine co-exposure consistent with an increase in CYP450-mediated dearylation (detoxification) versus desulfuration. It was of interest to note that the impact of nicotine co-exposure was experimentally observed only after repeated CPF doses. Physiologically based pharmacokinetic model simulations of CPF-oxon concentrations in blood and brain were predicted to be lower in nicotine treated groups, which were simulated by increasing the dearylation Vmax based upon previously conducted in vitro metabolism studies. These results were consistent with the experimental data. The current study demonstrated that repeated nicotine exposure could alter CPF metabolism in vivo, further modulating brain AChE inhibition.

Pharmacokinetics and effects on serum cholinesterase activities of organophosphorus pesticides acephate and chlorpyrifos in chimeric mice transplanted with human hepatocytes.

Science.gov (United States)

Suemizu, Hiroshi; Sota, Shigeto; Kuronuma, Miyuki; Shimizu, Makiko; Yamazaki, Hiroshi

2014-11-01

Organophosphorus pesticides acephate and chlorpyrifos in foods have potential to impact human health. The aim of the current study was to investigate the pharmacokinetics of acephate and chlorpyrifos orally administered at lowest-observed-adverse-effect-level doses in chimeric mice transplanted with human hepatocytes. Absorbed acephate and its metabolite methamidophos were detected in serum from wild type mice and chimeric mice orally administered 150mg/kg. Approximately 70% inhibition of cholinesterase was evident in plasma of chimeric mice with humanized liver (which have higher serum cholinesterase activities than wild type mice) 1day after oral administrations of acephate. Adjusted animal biomonitoring equivalents from chimeric mice studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Estimated plasma concentrations of acephate and chlorpyrifos in humans were consistent with reported concentrations. Acephate cleared similarly in humans and chimeric mice but accidental/incidental overdose levels of chlorpyrifos cleared (dependent on liver metabolism) more slowly from plasma in humans than it did in mice. The data presented here illustrate how chimeric mice transplanted with human hepatocytes in combination with a simple PBPK model can assist evaluations of toxicological potential of organophosphorus pesticides. Copyright © 2014 Elsevier Inc. All rights reserved.

Acute responses of American kestrels to methyl parathion and fenvalerate

Science.gov (United States)

Rattner, B.A.; Franson, J.C.

1984-01-01

Physiological and toxicological effects of p.o, methyl parathion (0.375-3.0 mg/kg) or fenvalerate (1000-4000 mg/kg) were examined over a 10 h period in American kestrels (Falco sparverius) maintained in thermoneutral (22?.C) and cold (-5?.C) environments. Methyl parathion was highly toxic (LD50=3.08 mg/kg, 95% confidence limits=2.29-4.l4 mg/kg, producing overt intoxication (abnormal posture, ataxia, paresis), dose-dependent inhibition (26-67%) of brain acetylcholinesterase activity, hyperglycemia, and elevated plasma corticosterone concentration. Transient but pronounced hypothermia was associated with plasma cholinesterase inhibition in excess of 50% (2 h after intubation), although this response was highly variable (plasma ChE inhibition vs. A cloacal temperature, r=-0.60). Fenvalerate, at doses far exceeding those encountered in the environment, caused mild intoxication (irregular head movement) and elevated plasma alanine aminotransferase activity, but did not alter cloacal temperature, plasma activities of CK, U-HBDH, and LDK, or concentrations of corticosterone, glucose, triiodothyronine, and uric acid. Cold exposure intensified methyl parathion toxicity, but did not affect that of fenvalerate. It would thus appear that the organophosphorus insecticide methyl parathion poses far greater hazard than the pyrethroid fenvalerate to raptorial birds.

Noi siamo quello che ricordiamo - Le frazze di Crucoli: il teatro, il rito, il riscatto sociale

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Tonia Mingrone

2012-01-01

Full Text Available Abstract - IT Questo lavoro nasce da una ricerca di campo sulle frazze, termine dialettale che indica le farse di Carnevale che si rappresentavano fino a cinquant’anni fa in molti paesi calabresi, tra cui il mio, Crucoli, in provincia di Crotone. Lo scopo di questo lavoro non è fare un resoconto esaustivo di tutto ciò che accadeva a Crucoli durante la celebrazione del Carnevale, impresa assai difficile dal momento che non ci sono documenti scritti e quindi bisogna affidarsi ai racconti orali delle persone intervistate, spesso non fedeli alla realtà, perché modificati dal tempo e dalla memoria. L’approccio con cui ho intrapreso questa ricerca è sicuramente legato all’aspetto teatrale e performativo dell’evento, senza trascurarne la rilevanza antropologica. Il materiale raccolto è frutto di interviste e colloqui con la gente del posto unito ad un grande lavoro di ricerca bibliografica di autori che avevano trattato di questo argomento in relazione ai loro paesi di origine.Lo scopo è quello di delineare l’organizzazione e lo svolgimento delle frazze, cercando di ricostruire la sua durata e le ripercussioni sulla comunità, nonché dimostrare ancora una volta come il teatro, messo a disposizione di alcuni eventi, diventi un mezzo forte di liberazione e di contestazione. Abstract - FR Cet article prend sa naissance par une recherche sur champ concernant les frazze, terme dialectal qui dénote les farces du Carnaval mises en scène jusqu'à il y a cinquante ans dans plusieurs villages en Calabria, entre eux le mien, Crucoli, dans la province de Crotone. La raison de ce travail n'est pas d'accomplir un compte rendu exhaustif de tout ce qui avait lieu à Crucoli pendant la célébration du Carnaval, l'exploit étant très difficile, du moment qu'aucun document écrit a été parvenu et par conséquence il est nécessaire de se remettre aux contes des témoins interviewés, souvent pas fidèles au réel, parce-que détournés par les

Cholinesterase inhibitors in Alzheimer's disease and Lewy body spectrum disorders: the emerging pharmacogenetic story

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Lam Benjamin

2009-12-01

Full Text Available Abstract This review provides an update on the current state of pharmacogenetic research in the treatment of Alzheimer's disease (AD and Lewy body disease (LBD as it pertains to the use of cholinesterase inhibitors (ChEI. AD and LBD are first reviewed from clinical and pathophysiological perspectives. This is followed by a discussion of ChEIs used in the symptomatic treatment of these conditions, focusing on their unique and overlapping pharmacokinetic and pharmacodynamic profiles, which can be used to identify candidate genes for pharmacogenetics studies. The literature published to date is then reviewed and limitations are discussed. This is followed by a discussion of potential endophenotypes which may help to refine future pharmacogenetic studies of response and adverse effects to ChEIs.

Proline-Based Carbamates as Cholinesterase Inhibitors

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Hana Pizova

2017-11-01

Full Text Available Series of twenty-five benzyl (2S-2-(arylcarbamoylpyrrolidine-1-carboxylates was prepared and completely characterized. All the compounds were tested for their in vitro ability to inhibit acetylcholinesterase (AChE and butyrylcholinesterase (BChE, and the selectivity of compounds to individual cholinesterases was determined. Screening of the cytotoxicity of all the compounds was performed using a human monocytic leukaemia THP-1 cell line, and the compounds demonstrated insignificant toxicity. All the compounds showed rather moderate inhibitory effect against AChE; benzyl (2S-2-[(2-chlorophenylcarbamoyl]pyrrolidine-1-carboxylate (IC50 = 46.35 μM was the most potent agent. On the other hand, benzyl (2S-2-[(4-bromophenyl-] and benzyl (2S-2-[(2-bromophenylcarbamoyl]pyrrolidine-1-carboxylates expressed anti-BChE activity (IC50 = 28.21 and 27.38 μM, respectively comparable with that of rivastigmine. The ortho-brominated compound as well as benzyl (2S-2-[(2-hydroxyphenylcarbamoyl]pyrrolidine-1-carboxylate demonstrated greater selectivity to BChE. The in silico characterization of the structure–inhibitory potency for the set of proline-based carbamates considering electronic, steric and lipophilic properties was provided using comparative molecular surface analysis (CoMSA and principal component analysis (PCA. Moreover, the systematic space inspection with splitting data into the training/test subset was performed to monitor the statistical estimators performance in the effort to map the probability-guided pharmacophore pattern. The comprehensive screening of the AChE/BChE profile revealed potentially relevant structural and physicochemical features that might be essential for mapping of the carbamates inhibition efficiency indicating qualitative variations exerted on the reaction site by the substituent in the 3′-/4′-position of the phenyl ring. In addition, the investigation was completed by a molecular docking study of recombinant human AChE.

Formulation and In-vivo Pharmacokinetic Consideration of Intranasal Microemulsion and Mucoadhesive Microemulsion of Rivastigmine for Brain Targeting.

Science.gov (United States)

Shah, Brijesh; Khunt, Dignesh; Misra, Manju; Padh, Harish

2018-01-02

Presence of tight junctions in blood brain barrier (BBB) pose a major hurdle for delivery of drug and severely affects adequate therapeutic concentration to reach the brain. In present work, we have selected Rivastigmine hydrogen tartrate (RHT), a reversible cholinesterase inhibitor, which exhibits extensive first-pass metabolism, resulting in limited absolute bioavailability (36%). RHT shows extremely low aqueous solubility and poor penetration, resulting in inadequate concentration reaching the brain, thus necessitating frequent oral dosing. To overcome these problems of RHT, microemulsion (ME) and mucoadhesive microemulsion (MME) of RHT were formulated for brain targeting via intranasal delivery route and compared on the basis of in vivo pharmacokinetics. ME and MME formulations containing RHT were developed by water titration method. Characterization of ME and MME was done for various physicochemical parameters, nasal spray pattern, and in vivo pharmacokinetics quantitatively and qualitatively (gamma scintigraphy studies). The developed ME and MME were transparent having globule size approximately in the range of 53-55 nm. Pharmacokinetic studies showed higher values for C max and DTP for intranasal RHT: CH-ME over RHT-ME, thus indicating the effect of chitosan in modulating tight junctions, thereby enhanced paracellular transport of RHT. Gamma scintigraphy and in vivo pharmacokinetic study suggested enhanced RHT concentration, upon intranasal administration of RHT:CH-ME, compare with other groups administered formulations intranasally. These findings suggested the potential of non-invasive intranasal route for brain delivery, especially for therapeutics, facing challenges in oral administration.

The Crèche and School structure of the CERN Staff Association is looking for a new name

CERN Multimedia

Staff Association

2018-01-01

The CERN Staff Association is launching a competition to find a new name to replace the current acronym EVEE (Espace de Vie Enfantine et École). The competition is open to everyone from Thursday, 1 February 2018 to Thursday, 15 March. All participants can send their name suggestions via the form available on the websites of the Staff Association and the Crèche and School. Good luck to all – may the best one win! P.S. The Rules of the Competition are available on both websites

Review: Thomas Bierschenk and Eva Spies (eds, 50 Jahre Unabhängigkeit in Afrika: Kontinuitäten, Brüche, Perspektiven (2012

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Geert Castryck

2015-01-01

Full Text Available Review of the edited volume: Thomas Bierschenk and Eva Spies (eds, 50 Jahre Unabhängigkeit in Afrika: Kontinuitäten, Brüche, Perspektiven, Cologne: Rüdiger Köppe Verlag, 2012, ISBN 9783896458292, 572 pages

Blood biochemical studies on toxicological aspects of dicophane pesticide in gamma irradiated rats

International Nuclear Information System (INIS)

Tawfik, S.M.F.

2003-01-01

The present work deals with the effect of feeding 150 mg dicophane/ kg, an organochlorine pesticide, and / or 6 Gy whole body gamma irradiation on albino rats which produced several alternations in blood biochemical components. Alkaline phosphatase (AP), cholinesterase (ChE), creatinine and urea were increased significantly for dicophane and or gamma irradiation treatment, while protein level was increased after dicophane treatment and decreased by radiation. On the other hand, serum levels of bilirubin tended to decrease allover the experimental periods. Dicophane feeding caused decrease in cholesterol and glucose levels till 7 and 15 days, respectively, then increased significantly after 30 days, and also significant increase were observed in their levels after dicophane and/ or gamma irradiation treatments

[sup 14]C-labeling of a tetrahydroacridine, a novel CNS-selective cholinesterase inhibitor

Energy Technology Data Exchange (ETDEWEB)

Nishioka, Kazuhiko; Kamada, Takeshi; Kanamaru, Hiroshi (Sumitomo Chemical Co., Ltd., Takatsukasa, Takarazuka (Japan). Environmental Health Science Lab.)

1992-06-01

9-Amino-8-fluoro-2,4-methano-1,2,3,4-tetrahydroacridine citrate (SM-10888), a novel cholinesterase inhibitor, was labeled with carbon-14 at C9 of the tetrahydroacridine ring for use in metabolic studies. Carbonation of 2,6-difluorophenyllithium (3) with [[sup 14]C]carbon dioxide gave the acid (4). Chlorination of 4 followed by treatment of the resulting acid chloride with ammonia afforded the amide (5). Dehydration of 5 with thionyl chloride and subsequent displacement reaction with ammonia gave the aminobenzonitrile (7). Condensation of 7 with the ketone (8) in the presence of anhydrous zinc chloride yielded the aminoacridine (9), which was treated with citric acid to afford [9-[sup 14]C]SM-10888 (1). The overall yield of 1 was 37% from 2, and the specific activity was 1.35 GBq/mmol. (author).

Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs.

Science.gov (United States)

Ramsay, Rona R; Tipton, Keith F

2017-07-15

The actions of many drugs involve enzyme inhibition. This is exemplified by the inhibitors of monoamine oxidases (MAO) and the cholinsterases (ChE) that have been used for several pharmacological purposes. This review describes key principles and approaches for the reliable determination of enzyme activities and inhibition as well as some of the methods that are in current use for such studies with these two enzymes. Their applicability and potential pitfalls arising from their inappropriate use are discussed. Since inhibitor potency is frequently assessed in terms of the quantity necessary to give 50% inhibition (the IC 50 value), the relationships between this and the mode of inhibition is also considered, in terms of the misleading information that it may provide. Incorporation of more than one functionality into the same molecule to give a multi-target-directed ligands (MTDLs) requires careful assessment to ensure that the specific target effects are not significantly altered and that the kinetic behavior remains as favourable with the MTDL as it does with the individual components. Such factors will be considered in terms of recently developed MTDLs that combine MAO and ChE inhibitory functions.

Chagas disease: modulation of the inflammatory response by acetylcholinesterase in hematological cells and brain tissue.

Science.gov (United States)

Silva, Aniélen D; Bottari, Nathieli B; do Carmo, Guilherme M; Baldissera, Matheus D; Souza, Carine F; Machado, Vanessa S; Morsch, Vera M; Schetinger, Maria Rosa C; Mendes, Ricardo E; Monteiro, Silvia G; Da Silva, Aleksandro S

2018-01-01

Chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. This enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. Thus, the aim of this study was to investigate whether Trypanosoma cruzi infection can alter the activity of acetylcholinesterase and acetylcholine levels in mice, and whether these alterations are linked to the inflammatory cholinergic signaling pathway. Twenty-four mice were divided into two groups: uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12). The animals developed acute disease with a peak of parasitemia on day 7 post-infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post-infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase activity, and histopathology were analyzed. In total blood and brain, acetylcholinesterase activity decreased at both times. On the other hand, acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with the control group. Infection by T. cruzi increased acetylcholine and nitric oxide levels and histopathological damage in the brain of mice associated to increased myeloperoxidase activity. Therefore, an intense inflammatory response in mice with acute Chagas disease in the central nervous system caused an anti-inflammatory response by the activation of the cholinergic inflammatory pathway.

Cholinesterase inhibitory activity and structure elucidation of a new phytol derivative and a new cinnamic acid ester from Pycnanthus angolensis

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Taiwo O. Elufioye

Full Text Available ABSTRACT The leaves of Pycnanthus angolensis (Welw. Warb., Myristicaceae, are used as memory enhancer and anti-ageing in Nigerian ethnomedicine. This study aimed at evaluating the cholinesterase inhibitory property as well as isolates the bioactive compounds from the plant. The acetylcholinesterase and butyrylcholinesterase inhibitory potentials of extracts, fractions, and isolated compounds were evaluated by colorimetric and TLC bioautographic assay techniques. The extract inhibited both enzymes with activity increasing with purification, ethyl acetate fraction being most active fraction at 65.66 ± 1.06% and 49.38 ± 1.66% against acetylcholinesterase and butyrylcholinesterase, respectively while the supernatant had 77.44 ± 1.18 inhibition against acetylcholinesterase. Two new bioactive compounds, (2E, 18E-3,7,11,15,18-pentamethylhenicosa-2,18-dien-1-ol (named eluptol and [12-(4-hydroxy-3-methyl-oxo-cyclopenta-1,3-dien-1yl-11-methyl-dodecyl](E-3-(3,4-dimethylphenylprop-2-enoate (named omifoate A were isolated from the plant with IC50 of 22.26 µg/ml (AChE, 34.61 µg/ml (BuChE and 6.51 µg/ml (AChE, 9.07 µg/ml (BuChE respectively. The results showed that the plant has cholinesterase inhibitory activity which might be responsible for its memory enhancing action, thus justifying its inclusion in traditional memory enhancing preparations

Design, synthesis and biological evaluation of phthalimide-alkylamine derivatives as balanced multifunctional cholinesterase and monoamine oxidase-B inhibitors for the treatment of Alzheimer's disease.

Science.gov (United States)

Sang, Zhipei; Wang, Keren; Wang, Huifang; Yu, Lintao; Wang, Huijuan; Ma, Qianwen; Ye, Mengyao; Han, Xue; Liu, Wenmin

2017-11-15

A series of novel phthalimide-alkylamine derivatives were synthesized and evaluated as multi-functions inhibitors for the treatment of Alzheimer's disease (AD). The results showed that compound TM-9 could be regarded as a balanced multi-targets active molecule. It exhibited potent and balanced inhibitory activities against ChE and MAO-B (huAChE, huBuChE, and huMAO-B with IC 50 values of 1.2μM, 3.8μM and 2.6 μM, respectively) with low selectivity. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that TM-9 binds simultaneously to the catalytic active site and peripheral anionic site of AChE. Interestingly, compound TM-9 abided by Lipinski's rule of five. Furthermore, our investigation proved that TM-9 indicated weak cytotoxicity, and it could cross the blood-brain barrier (BBB) in vitro. The results suggest that compound TM-9, an interesting multi-targeted active molecule, offers an attractive starting point for further lead optimization in the drug-discovery process against Alzheimer's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Changes in mouse brain metabolism following a convulsive dose of soman: A proton HRMAS NMR study

Energy Technology Data Exchange (ETDEWEB)

Fauvelle, F. [Unite de Biophysique Cellulaire et Moleculaire, Institut de Recherche Biomedicale des Armees, Centre de Recherches du Service Sante des Armees, BP87, 38 702 La Tronche Cedex (France); Dorandeu, F.; Carpentier, P.; Foquin, A. [Departement de Toxicologie, Institut de Recherche Biomedicale des Armees, Centre de Recherches du Service Sante des Armees, 24 avenue des Maquis du Gresivaudan, BP87, 38 702 La Tronche Cedex (France); Rabeson, H.; Graveron-Demilly, D. [Universite Lyon 1, Laboratoire Creatis-LRMN, CNRS UMR 5220, INSERM U630, INSA de Lyon (France); Arvers, P. [Unite de Biophysique Cellulaire et Moleculaire, Institut de Recherche Biomedicale des Armees, Centre de Recherches du Service Sante des Armees, BP87, 38 702 La Tronche Cedex (France); Testylier, G., E-mail: guytestylier@crssa.net [Departement de Toxicologie, Institut de Recherche Biomedicale des Armees, Centre de Recherches du Service Sante des Armees, 24 avenue des Maquis du Gresivaudan, BP87, 38 702 La Tronche Cedex (France)

2010-01-12

Soman, an irreversible organophosphorus cholinesterase inhibitor, induces status epilepticus and, in sensitive brain areas, seizure-related brain damage (e.g. brain edema and neuronal loss). The brain metabolic disturbances associated with these events are ill known. In the present study, we thus evaluated these changes in a murine model of soman-induced status epilepticus up to 7 days after intoxication. Mice, protected by HI-6 and atropine methyl nitrate, were poisoned with soman (172 μg/kg) and then sacrificed at set time points, from 1 h to 7 days. Brain biopsies from the piriform cortex (Pir) and cerebellum (Cer) were analyzed by {sup 1}H HRMAS NMR spectroscopy. Spectra were then analyzed using both a supervised multivariate analysis and the QUEST procedure of jMRUI for the quantification of 17 metabolites. The multivariate analysis clearly showed the metabolic differences between a damaged structure (Pir) and a structure with less prominent changes (cerebellum) and helped to globally assess the time course of metabolic changes. Analysis of the individual metabolites showed that the major changes took place in the piriform cortex but that cerebellum was not change-free. The most prominent changes in the former were an early (1-4 h) increase in alanine and acetate, a delayed increase in lactate, glycerophosphocholine and glutamine as well as a delayed decrease in myo-inositol and N-acetylaspartate. A week after poisoning, some metabolic disturbances were still present. Further research will be necessary to clarify what could be the involvement of these metabolites in physiological processes and how they might become useful surrogate markers of brain damage and repair.

Changes in mouse brain metabolism following a convulsive dose of soman: A proton HRMAS NMR study

International Nuclear Information System (INIS)

Fauvelle, F.; Dorandeu, F.; Carpentier, P.; Foquin, A.; Rabeson, H.; Graveron-Demilly, D.; Arvers, P.; Testylier, G.

2010-01-01

Soman, an irreversible organophosphorus cholinesterase inhibitor, induces status epilepticus and, in sensitive brain areas, seizure-related brain damage (e.g. brain edema and neuronal loss). The brain metabolic disturbances associated with these events are ill known. In the present study, we thus evaluated these changes in a murine model of soman-induced status epilepticus up to 7 days after intoxication. Mice, protected by HI-6 and atropine methyl nitrate, were poisoned with soman (172 μg/kg) and then sacrificed at set time points, from 1 h to 7 days. Brain biopsies from the piriform cortex (Pir) and cerebellum (Cer) were analyzed by 1 H HRMAS NMR spectroscopy. Spectra were then analyzed using both a supervised multivariate analysis and the QUEST procedure of jMRUI for the quantification of 17 metabolites. The multivariate analysis clearly showed the metabolic differences between a damaged structure (Pir) and a structure with less prominent changes (cerebellum) and helped to globally assess the time course of metabolic changes. Analysis of the individual metabolites showed that the major changes took place in the piriform cortex but that cerebellum was not change-free. The most prominent changes in the former were an early (1-4 h) increase in alanine and acetate, a delayed increase in lactate, glycerophosphocholine and glutamine as well as a delayed decrease in myo-inositol and N-acetylaspartate. A week after poisoning, some metabolic disturbances were still present. Further research will be necessary to clarify what could be the involvement of these metabolites in physiological processes and how they might become useful surrogate markers of brain damage and repair.

State-wide hospital clinical laboratory plan for measuring cholinesterase activity for individuals suspected of exposure to nerve agent chemical weapons.

Science.gov (United States)

Wu, Alan H B; Smith, Andrew; McComb, Robert; Bowers, George N; Makowski, Gregory S; McKay, Charles A; Vena, Jason; McDonagh, John; Hopfer, Sidney; Sena, Salvatore F; Malkus, Herbert; Forte, Elaine; Kelly, Katherine

2008-02-01

Hospital laboratories currently lack the capacity to provide emergency determination of cholinesterase activity. We have developed a hospital-based 3-tiered system to test plasma for butyrylcholinesterase (BChE) activity and whole blood for red cell acetylcholinesterase (AChE) activity using available technology and personnel. Interagency communications, toxidrome definition, and patient triage will be coordinated by the Connecticut Department of Public Health and the Poison Control Center. Initial BChE data documents good precision between institutions (coefficient of variation chemical terrorism or large scale HazMat events.

Nouvelles fonctions de l'agriculture et dynamiques des exploitations: une analyse chorématique dans les monts d'Ardèche

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Muriel Bonin

2001-06-01

Full Text Available Les modèles spatiaux sont utilisés pour l'analyse des trajectoires d'exploitations agricoles pour mettre en évidence les liens entre les transformations socio-économiques et les dynamiques de territoires. Les traits de dynamiques spatiales sont identifiés et utilisés pour analyser l'impact de l'introduction de l'agritourisme dans les exploitations dans le Parc naturel régional des monts d'Ardèche.

RESISTENCIA MICROBIANA EN EL CARDIOCENTRO ERNESTO CHE GUEVARA. ESTUDIO DE 5 AÑOS / Microbial resistance at the “Ernesto Che Guevara” Cardiology Hospital. A five year study

Directory of Open Access Journals (Sweden)

Nérida Rodríguez Oliva

2009-06-01

Full Text Available Introduction and Objectives: The appearance of nosocomial bacterial resistance represents a problem of growing concern because it largely affects the evolution of patients and the health resources devoted to it. The objective of this work was to determine the most common germs and their microbial resistance. Methods: A descriptive retrospective study was carried out analyzing the result of the isolation of germs from all type of secretions and from the blood cultures of a group ofpatients hospitalized at the Ernesto Che Guevara Cardiology Hospital in a five year period. Results: A total of 397 strains were isolated, 77 Staphylococcus aureus and 320 Enterobacteriaceae. The former presented 100% resistance to penicillin. The Staphylococcus sensitive to methicillin presented 4.9 % resistance to cotrimoxazole and gentamicin. The strains resistant to methicillin or oxacillin had a high resistance to gentamicin (87.5 % and ciprofloxacin (81.2 %, a medium resistance to cefazolin and oxacilline (20.5 %, and just 12.5 percent resistance to cotrimoxazole. Conclusions: the Staphylococcus aureus and the Enterobacteriaceae were the most common germs. The preoperative prophylaxis in these patients must not be done with cefazolin as a routine because the staphylococci resistant to methicillin or oxacillin have influence on other antimicrobials.

Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman

International Nuclear Information System (INIS)

Churchill, L.; Pazdernik, T.L.; Jackson, J.L.; Nelson, S.R.; Samson, F.E.; McDonough, J.H. Jr.

1984-01-01

[3H]Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturation curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without any significant change in affinity. These brain areas showing significant decrements in muscarinic receptors recovered with a similar time course. An estimate of the time for 50% recovery for some of the brain areas was 14 days for superior colliculus, 16 days for cortex, and 19 days for hippocampal body. The application of quantitative receptor autoradiography to analyze receptor alterations has been valuable in localizing the telencephalon as a region more susceptible to change in receptor concentration

Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman

Energy Technology Data Exchange (ETDEWEB)

Churchill, L.; Pazdernik, T.L.; Jackson, J.L.; Nelson, S.R.; Samson, F.E.; McDonough, J.H. Jr.

1984-08-01

(3H)Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturation curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without any significant change in affinity. These brain areas showing significant decrements in muscarinic receptors recovered with a similar time course. An estimate of the time for 50% recovery for some of the brain areas was 14 days for superior colliculus, 16 days for cortex, and 19 days for hippocampal body. The application of quantitative receptor autoradiography to analyze receptor alterations has been valuable in localizing the telencephalon as a region more susceptible to change in receptor concentration.

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

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Bautista-Aguilera OM

2014-10-01

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

RBC acetyl cholinesterase: A poor man′s early diagnostic biomarker for familial alzheimer′s and Parkinson′s disease dementia

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Himmatrao Saluba Bawaskar

2015-01-01

Full Text Available Objective: Analysis of red blood cell acetyl cholinesterase (AChE in a familial Alzheimer′s diseases (AD Parkinson′s disease dementia (PDD and their first generation. Setting: General hospital, Mahad district, Raigad. Patients and Methods: Clinically diagnosed patients of AD and PDD and their asymptomatic relatives. Their blood was collected in EDTA tube and transferred to laboratory at Mumbai. Result: Median red blood cell (RBC cholinesterase levels amongst PDD, their first generation asymptomatic relatives, familial AD, asymptomatic relatives of AD, healthy controls, farmers exposed to pesticides (positive control and other neurological condition without dementia (hypertension with TIA 1, sub-dural hematoma 2, hypothyroid 1, non-familial unilateral parkinsonism without dementia 3, writers cramps 2, hyponitremia 1 and cerebral palsy with non-fluent aphasia 1. Median values of RBC AChE were 19086.78 U/L, 15666.05 U/L, 9013.11 U/L, 7806.19 U/L, 14334.57 U/L, 9785.05 U/L and 13162.60 U/L, respectively. As compared to controls, RBC AChE levels were statistically significant among PDD (P = 0.004 and significantly lowered among familial AD patients (P = 0.010, relatives of patients (P = 0.010. Interpretations: Below the normal RBC AChE level is a potential biomarker in asymptomatic relatives of familial AD patients. RBC AChE is raised than normal level in patients suffering from PDD, where AChE inhibitors are helpful. However, RBC AChE level below the normal where AChE inhibitor may not be effective.

Planarian cholinesterase: in vitro characterization of an evolutionarily ancient enzyme to study organophosphorus pesticide toxicity and reactivation.

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Hagstrom, Danielle; Hirokawa, Hideto; Zhang, Limin; Radic, Zoran; Taylor, Palmer; Collins, Eva-Maria S

2017-08-01

The freshwater planarian Dugesia japonica has recently emerged as an animal model for developmental neurotoxicology and found to be sensitive to organophosphorus (OP) pesticides. While previous activity staining of D. japonica, which possess a discrete cholinergic nervous system, has shown acylthiocholine catalysis, it is unknown whether this is accomplished through an acetylcholinesterase (AChE), butyrylcholinesterase (BChE), or a hybrid esterase and how OP exposure affects esterase activity. Here, we show that the majority of D. japonica cholinesterase (DjChE) activity departs from conventional AChE and BChE classifications. Inhibition by classic protonable amine and quaternary reversible inhibitors (ethopropazine, donepezil, tacrine, edrophonium, BW284c51, propidium) shows that DjChE is far less sensitive to these inhibitors than human AChE, suggesting discrete differences in active center and peripheral site recognition and structures. Additionally, we find that different OPs (chlorpyrifos oxon, paraoxon, dichlorvos, diazinon oxon, malaoxon) and carbamylating agents (carbaryl, neostigmine, physostigmine, pyridostigmine) differentially inhibit DjChE activity in vitro. DjChE was most sensitive to diazinon oxon and neostigmine and least sensitive to malaoxon and carbaryl. Diazinon oxon-inhibited DjChE could be reactivated by the quaternary oxime, pralidoxime (2-PAM), and the zwitterionic oxime, RS194B, with RS194B being significantly more potent. Sodium fluoride (NaF) reactivates OP-DjChE faster than 2-PAM. As one of the most ancient true cholinesterases, DjChE provides insight into the evolution of a hybrid enzyme before the separation into distinct AChE and BChE enzymes found in higher vertebrates. The sensitivity of DjChE to OPs and capacity for reactivation validate the use of planarians for OP toxicology studies.

rCBF and cognitive impairment changes assessed by SPECT and ADAS-cog in late-onset Alzheimer's disease after 18 months of treatment with the cholinesterase inhibitors donepezil or galantamine.

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Shirayama, Yukihiko; Takahashi, Michio; Oda, Yasunori; Yoshino, Kouhei; Sato, Koichi; Okubo, Toshiyuki; Iyo, Masaomi

2017-12-15

Late-onset Alzheimer's disease (AD) differs substantially from early-onset AD. In this cross sectional study we investigated brain perfusion changes after 18 months of treatment with cholinesterase inhibitors (ChEIs) donepezil or galantamine. Twenty-five drug-naïve late-onset AD patients were recruited from outpatient clinics. We examined brain perfusion using single photon emission computed tomography (SPECT) and used three-dimensional stereotactic surface projection (3D-SSP) and the stereotactic extraction estimation method (SEE) level 3 to analyze classified gyrus level segments. We assessed cognitive function using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) grouped into three subgroup domains, language, memory, and praxis. In the follow-up data, some regions were further hypoperfused, reflecting worsening of the disease, while other regions showed alleviated hypoperfusion, potentially related to the ChEIs treatment. Regional cerebral blood flow (rCBF) decreased in the parietal cortex and increased in the frontal and the limbic cortices. Increased hypoperfusion significantly correlated with ADAS-cog scores changes were seen in the superior parietal lobule, inferior parietal lobule, angular gyrus, and supramarginal gyrus of the parietal cortex. Alleviated hypoperfusion significantly related to recovery of ADAS-cog scores were seen in the rectal and paracentral lobule of the frontal cortex, and the anterior cingulate of the limbic cortex. These regions showed significant relationships with total ADAS-cog and language, memory and praxis subscales scores. The current longitudinal study indicates prominent rCBF changes and their relationships with changes in ADAS-cog scores in late-onset AD patients.

The relationship between total cholinesterase activity and mortality in four butterfly species

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Bargar, Timothy A.

2012-01-01

The relationship between total cholinesterase activity (TChE) and mortality in four butterfly species (great southern white [Ascia monuste], common buckeye [Junonia coenia], painted lady [Vanessa cardui], and julia butterflies [Dryas julia]) was investigated. Acute contact toxicity studies were conducted to evaluate the response (median lethal dose [LD50] and TChE) of the four species following exposure to the organophosphate insecticide naled. The LD50 for these butterflies ranged from 2.3 to 7.6 μg/g. The average level of TChE inhibition associated with significant mortality ranged from 26 to 67%, depending on the species. The lower bounds of normal TChE activity (2 standard deviations less than the average TChE for reference butterflies) ranged from 8.4 to 12.3 μM/min/g. As a percentage of the average reference TChE activity for the respective species, the lower bounds were similar to the inhibition levels associated with significant mortality, indicating there was little difference between the dose resulting in significant TChE inhibition and that resulting in mortality.

Start of enrolment for the Champs-Fréchets crèche (EVE)

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HR Department

2008-01-01

As announced in Bulletin 43/2007, CERN signed an agreement with the commune of Meyrin on 17 October 2007 under which 20 places will be reserved for the children of CERN personnel in the Champs-Fréchets day care centre (EVE), which will open on Monday, 25 August, and CERN will contribute to the funding. This agreement allows members of the CERN personnel (employees and associates) access to the crèche, for children aged between 4 months and 4 years, irrespective of where they are living. Applications for the school year starting autumn 2008 will be accepted from Monday 17 March until Monday 30 June 2008. Members of the personnel must complete the enrolment formalities with the Meyrin infant education service themselves: Mairie de Meyrin Service de la Petite Enfance 2 rue des Boudines Case postale 367 - 1217 Meyrin 1 - Tel. + 41 (0)22 782 21 21 mailto:meyrin@meyrin.ch http://www.meyrin.ch/petiteenfance Application forms (in PDF) can be downloaded from the website of the com...

Aqueous extracts of avocado pear (Persea americana Mill.) leaves and seeds exhibit anti-cholinesterases and antioxidant activities in vitro.

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Oboh, Ganiyu; Odubanjo, Veronica O; Bello, Fatai; Ademosun, Ayokunle O; Oyeleye, Sunday I; Nwanna, Emem E; Ademiluyi, Adedayo O

2016-03-01

Avocado pear (Persea americana Mill.) leaves and seeds are used in traditional medicine for the treatment/management of Alzheimer disease (AD); however, information on the mechanism of actions is limited. This study sought to investigate the effect of P. americana leaf and seed aqueous extracts on some enzymes linked with AD (acetylcholinesterase [AChE] and butyrylcholinesterase [BChE] activities) and their antioxidant potentials in vitro. The inhibitory effects of extracts on AChE and BChE activities and antioxidant potentials (inhibition of Fe2+- and sodium nitroprusside-induced thiobarbiturate reactive species [TBARS] production in rat brain homogenates, radicals [1,1-diphenyl-2-picrylhydrazyl, hydroxyl, and nitric oxide] scavenging and iron [Fe] chelation abilities) were investigated. Phenolic content and phytochemical screening were carried out. Alkaloid profile was also determined using gas chromatography coupled with flame ionization detector (GC-FID). The extracts inhibited AChE and BChE activities and prooxidant-induced TBARS production in a dose-dependent manner, with the seed extract having the highest inhibitory effect and the leaf extract exhibiting higher phenolic content and radical scavenging abilities, but lower Fe chelation ability compared with that of the seed. The phytochemical screening revealed the presence of saponins, alkaloids, and terpenoids in both extracts, whereas the total alkaloid profile was higher in the seed extract than in the leaf extract, as revealed by GC-FID. The anti-cholinesterase and antioxidant activities of avocado leaf and seed could be linked to their phytoconstituents and might be the possible mechanisms underlying their use as a cheap and natural treatment/management of AD. However, these extracts should be further investigated in vivo.

[Comparative analysis of sensitivity of proteases (chymotrypsin and trypsin) and cholinesterases of different origin to some organophosphorus inhibitors].

Science.gov (United States)

Rozengart, E V

2009-01-01

The antichymotrypsin, antitrypsin, and anticholinesterase efficiencies of four homologous series of organophosphorus inhibitors are compared: O-ethyl-S-(n-alkyl)methylthiophosphonates, O-(n-alkyl)-S-(n-butyl)methylthiophosphonates, O-(n-alkyl)-S-beta-(ethylmercaptoethylene)methylthiophosphonates, and their methylsulfomethylates. As sources of a-chymotrypsin and trypsin, commercial compounds of Worthington Biochemical Corporation and Leningrad Myasokombinat were tested. Bimolecular constant of the reaction rate was used as the measure of antienzyme efficiency. In all cases, the antichymotrypsin efficiency was lower, while the antitrypsin--essentially higher than the anticholinesterase activity of the studied inhibitors. These differences were found to much depend both on the inhibitor structure and on nature of the cholinesterase compounds.

Molecular assembly and biosynthesis of acetylcholinesterase in brain and muscle: The roles of t-peptide, FHB domain and N-linked glycosylation

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Vicky P. Chen

2011-10-01

Full Text Available Acetylcholinesterase (AChE is responsible for the hydrolysis of the neurotransmitter, acetylcholine, in the nervous system. The functional localization and oligomerization of AChE T variant are depending primarily on the association of their anchoring partners, either collagen tail (ColQ or proline rich membrane anchor (PRiMA. Complexes with ColQ represent the asymmetric forms (A12 in muscle, while complexes with PRiMA represent tetrameric globular forms (G4 mainly found in brain and muscle. Apart from these traditional molecular forms, a ColQ-linked asymmetric form and a PRiMA-linked globular form of hybrid cholinesterases (ChEs, having both AChE and BChE catalytic subunits, were revealed in chicken brain and muscle. The similarity of various molecular forms of AChE and BChE raises interesting question regarding to their possible relationship in enzyme assembly and localization. The focus of this review is to provide current findings about the biosynthesis of different forms of ChEs together with their anchoring proteins.

Oral supplements of inulin during gestation offsets rotenone-induced oxidative impairments and neurotoxicity in maternal and prenatal rat brain.

Science.gov (United States)

Krishna, Gokul; Muralidhara

2018-05-25

Environmental insults including pesticide exposure and their entry into the immature brain are of increased concern due to their developmental neurotoxicity. Several lines of evidence suggest that maternal gut microbiota influences in utero fetal development via modulation of host's microbial composition with prebiotics. Hence we examined the hypothesis if inulin (IN) supplements during pregnancy in rats possess the potential to alleviate brain oxidative response and mitochondrial deficits employing a developmental model of rotenone (ROT) neurotoxicity. Initially, pregnant Sprague-Dawley rats were gavaged during gestational days (GDs) 6-19 with 0 (control), 10 (low), 30 (mid) or 50 (high) mg/kg bw/day of ROT to recapitulate developmental effects on general fetotoxicity (assessed by the number of fetuses, fetal body and placental weights), markers of oxidative stress and cholinergic activities in maternal brain regions and whole fetal-brain. Secondly, dams orally supplemented with inulin (2×/day, 2 g/kg/bw) on GD 0-21 were administered ROT (50 mg/kg, GD 6-19). IN supplements increased maternal cecal bacterial numbers that significantly corresponded with improved exploratory-related behavior among ROT administered rats. In addition, IN supplements improved fetal and placental weight on GD 19. IN diminished gestational ROT-induced increased reactive oxygen species levels, protein and lipid peroxidation biomarkers, and cholinesterase activity in maternal brain regions (cortex, cerebellum, and striatum) and fetal brain. Moreover, in the maternal cortex, mitochondrial assessment revealed IN protected against ROT-induced reduction in NADH cytochrome c oxidoreductase and ATPase activities. These data suggest a potential role for indigestible oligosaccharides in reducing oxidative stress-mediated developmental origins of neurodegenerative disorders. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical and radiological effects of chronic ingestion of uranium in the rat brain: biochemical impairment of dopaminergic, serotonergic and cholinergic neuro-transmissions

International Nuclear Information System (INIS)

Bussy, C.

2005-09-01

Uranium is an environmental ubiquitous metal-trace element. It has both chemical and radiological toxicity. After chronic ingestion, uranium can distribute in any part of the body and accumulate in the brain. The aims of this study was 1) to determine and estimate the effects of uranium on dopaminergic, serotoninergic and cholinergic systems and 2) to measure the uranium amount in the brain, after chronic exposure by ingestion of depleted (D.U.) or enriched (E.U.) uranium during 1.5 to 18 months at 40 mg.L -1 (40 ppm) in different rat brain areas. At any time of exposure, the results show that both the neurotransmission alterations and the uranium brain accumulation were moderate, area specific, time-evolutive and depended on uranium specific activity. After D.U. exposure, monoamine perturbations are chronic and progressive. On the contrary, monoamine alterations occurred only after long term of E.U. exposure. These mono-aminergic modifications are not always dependent on uranium accumulation in brain areas. Moreover, although the cholinergic system was not affected at both 1.5 and 9 months of D.U. exposure, the alteration of ChE activity after E.U. exposure are both dependent on uranium accumulation in brain areas and on uranium specific activity. After E.U. exposure, cholinergic modification and uranium accumulation in hippocampus could partially explain the short-term memory disturbances which have been previously reported. (author)

Bioscavengers for the protection of humans against organophosphate toxicity.

Science.gov (United States)

Doctor, Bhupendra P; Saxena, Ashima

2005-12-15

Current antidotes for organophosphorus compounds (OP) poisoning consist of a combination of pretreatment with carbamates (pyridostigmine bromide), to protect acetylcholinesterase (AChE) from irreversible inhibition by OP compounds, and post-exposure therapy with anti-cholinergic drugs (atropine sulfate) to counteract the effects of excess acetylcholine and oximes (e.g., 2-PAM chloride) to reactivate OP-inhibited AChE. These antidotes are effective in preventing lethality from OP poisoning, but they do not prevent post-exposure incapacitation, convulsions, seizures, performance decrements, or in many cases permanent brain damage. These symptoms are commonly observed in experimental animals and are likely to occur in humans. The problems intrinsic to these antidotes stimulated attempts to develop a single protective drug, itself devoid of pharmacological effects, which would provide protection against the lethality of OP compounds and prevent post-exposure incapacitation. One approach is the use of enzymes such as cholinesterases (ChEs), beta-esterases in general, as single pretreatment drugs to sequester highly toxic OP anti-ChEs before they reach their physiological targets. This approach turns the irreversible nature of the OP: ChE interaction from disadvantage to an advantage; instead of focusing on OP as an anti-ChE, one can use ChE as an anti-OP. Using this approach, it was shown that administration of fetal bovine serum AChE (FBSAChE) or equine serum butyrylcholinesterase (EqBChE) or human serum BChE (HuBChE) protected the animals from multiple LD50s of a variety of highly toxic OPs without any toxic effects or performance decrements. The bioscavengers that have been explored to date for the detoxification of OPs fall into three categories: (A) those that can catalytically hydrolyze OPs and thus render them non-toxic, such as OP hydrolase and OP anhydrase; (B) those that stoichiometrically bind to OPs, that is, 1 mol of enzyme neutralizes one or 2 mol of OP

Determination of the Index of Consumption of Petroleum of the Calcining Kiln of the Ernesto Che Guevara Commander Undertaking

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Yarilys Gaínza-Delgado

2016-07-01

Full Text Available This work presents the results obtained in carrying out the mass and energy balances in the calcining kiln of the company commander Ernesto Che Guevara, for determining the consumption index of petroleum used for obtaining nickel oxide through thermal decomposition of the basic nickel carbonate. It was shown that for a production of basic nickel carbonate of              12 t / h with 69% moisture, it is necessary to feed about 1100 kg / h of fuel, for an consumption index of 91.67 kg of fuel per ton of load.

Differential swimming performance of two natricine snakes exposed to a cholinesterase-inhibiting pesticide

International Nuclear Information System (INIS)

Hopkins, W.A.; Winne, C.T.; DuRant, S.E.

2005-01-01

Environmental contaminants have direct effects on organisms at the molecular, cellular, and tissue levels, but the net results of these sub-organismal effects are only consequential to exposed populations if they alter organism-level traits that ultimately influence fitness (e.g., growth, locomotor performance, reproduction, and survival). Here, we explore the possibility that the swimming performance of neonate black swamp snakes (Seminatrix pygaea) and diamondback water snakes (Nerodia rhombifer) may be affected by exposure to carbaryl (2.5 and 5.0 mg/L). The highest concentration of carbaryl caused greater reductions in swim velocity in S. pygaea than in N. rhombifer. Most individuals recovered from the effects of carbaryl on swimming performance within 96 h, but recovery was significantly slower in S. pygaea than in N. rhombifer. We hypothesize that the sensitivity of S. pygaea may arise from its highly permeable integument compared to other natricines. Our findings suggest that performance can serve as an ecologically relevant response to contaminant exposure in reptiles and warrants further study. - Exposure to a cholinesterase inhibitor reduces swimming velocity in snakes

Differential swimming performance of two natricine snakes exposed to a cholinesterase-inhibiting pesticide

Energy Technology Data Exchange (ETDEWEB)

Hopkins, W.A. [University of Georgia, Savannah River Ecology Laboratory, Wildlife Ecotoxicology and Physiological Ecology Program, PO Drawer E, Aiken, SC 29802 (United States)]. E-mail: hopkins@srel.edu; Winne, C.T. [University of Georgia, Savannah River Ecology Laboratory, Wildlife Ecotoxicology and Physiological Ecology Program, PO Drawer E, Aiken, SC 29802 (United States); DuRant, S.E. [University of Georgia, Savannah River Ecology Laboratory, Wildlife Ecotoxicology and Physiological Ecology Program, PO Drawer E, Aiken, SC 29802 (United States)

2005-02-01

Environmental contaminants have direct effects on organisms at the molecular, cellular, and tissue levels, but the net results of these sub-organismal effects are only consequential to exposed populations if they alter organism-level traits that ultimately influence fitness (e.g., growth, locomotor performance, reproduction, and survival). Here, we explore the possibility that the swimming performance of neonate black swamp snakes (Seminatrix pygaea) and diamondback water snakes (Nerodia rhombifer) may be affected by exposure to carbaryl (2.5 and 5.0 mg/L). The highest concentration of carbaryl caused greater reductions in swim velocity in S. pygaea than in N. rhombifer. Most individuals recovered from the effects of carbaryl on swimming performance within 96 h, but recovery was significantly slower in S. pygaea than in N. rhombifer. We hypothesize that the sensitivity of S. pygaea may arise from its highly permeable integument compared to other natricines. Our findings suggest that performance can serve as an ecologically relevant response to contaminant exposure in reptiles and warrants further study. - Exposure to a cholinesterase inhibitor reduces swimming velocity in snakes.

Brain cancer and pesticide relationship in orchard farmers of Kashmir.

Science.gov (United States)

Bhat, Abdul Rashid; Wani, Muhammed Afzal; Kirmani, A R

2010-09-01

The increasing trend in the incidence of primary malignant brain tumors in orchard farmers and their families in Kashmir. To determine the relationship between the patients of primary malignant brain tumors and their occupation. Retrospectively, case files along with death certificates of 432 patients of primary malignant brain tumors and 457 controls (non-tumor neurologic diseases), admitted for treatment simultaneously over a period of 4 years from January 2005 to December 2008, to the Neurosurgery, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Kashmir, were studied. Follow-up and family interaction was established. Analysis revealed that 90.04% (389 out of 432) patients were orchard farm workers, orchard residents and orchard playing children exposed to the high levels of multiple types of neurotoxic and carcinogenic (chlorpyriphos, dimethoate, mancozeb and captan) chemicals for more than 10 years [relative risk (RR) = 10.6; odds ratio (OR) = >10; 95% confidence interval (CI) = >25-40]. The 9.96% (43 out of 432) patients were not exposed to pesticides. On the other hand, only 19 patients out of 457 controls had recorded history of pesticide exposure and 438 were unrelated to pesticides. Out of 389 patients, 71.7% (279 out of 389) were males and 28.3% (110 out of 389), including six members of three families, were females (one male child). All orchard-related 389 patients had high-grade tumors as compared to the non-pesticide tumors. Mortality in pesticide-exposed tumors was 12%. The higher or upper-normal levels of serum cholinesterase (AChE) were observed in 54.7% (213 out of 389) patients and decreased levels were found in only 45.3% (176 out of 389) orchard-related patients (RR = 19.4; OR = >5; 95% CI = >1-10). Although serum AChE levels were a routine investigation in malignant brain tumors, this was not a routine in other neurological conditions (hospitalized controls). The familial gliomas have shown an emerging trend in the orchard residents of

Coumarin derivatives bearing benzoheterocycle moiety: synthesis, cholinesterase inhibitory, and docking simulation study

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Kimia Hirbod

2017-06-01

Full Text Available Objective(s: To investigate the efficiency of a novel series of coumarin derivatives bearing benzoheterocycle moiety as novel cholinesterase inhibitors. Materials and Methods: Different 7-hydroxycoumarin derivatives were synthesized via Pechmann or Knoevenagel condensation and conjugated to different benzoheterocycle (8-hydroxyquinoline, 2-mercaptobenzoxazole or 2-mercaptobenzimidazole using dibromoalkanes 3a-m. Final compounds were evaluated against acetylcholinesterase (AChE and butyrylcholinesterase (BuChE by Ellman's method. Kinetic study of AChE inhibition and ligand-protein docking simulation were also carried out for the most potent compound 3b. Results: Some of the compounds revealed potent and selective activity against AChE. Compound 3b containing the quinoline group showed the best activity with an IC50 value of 8.80 µM against AChE. Kinetic study of AChE inhibition revealed the mixed-type inhibition of the enzyme by compound 3b. Ligand-protein docking simulation also showed that the flexibility of the hydrophobic five carbons linker allows the quinoline ring to form π-π interaction with Trp279 in the PAS. Conclusion: We suggest these synthesized compounds could become potential leads for AChE inhibition and prevention of AD symptoms.

Blood cholinesterase activity levels of farmers in winter and hot season of Mae Taeng District, Chiang Mai Province, Thailand.

Science.gov (United States)

Hongsibsong, Surat; Kerdnoi, Tanyaporn; Polyiem, Watcharapon; Srinual, Niphan; Patarasiriwong, Vanvimol; Prapamontol, Tippawan

2018-03-01

Organophosphate and carbamate pesticides have been widely used by farmers for crop protection and pest control. Inhibition of acetylcholinesterase (AChE) in erythrocyte and butyrylcholinesterase (BChE) in plasma is the predominant toxic effect of organophosphate and carbamate pesticides. Mae Taeng District, Chiang Mai Province, is one of the large areas of growing vegetables and fruits. Due to their regular exposure to these pesticides, the farmers are affected by this toxicity. The objective of the study was to examine the AChE and the BChE activity levels in the blood of 102 farmers for comparison of exposure in two cropping seasons, winter and hot. Blood samples were collected in December 2013 (winter) and April-June 2014 (hot). A total of 102 farmers joined the study, represented by 76 males (74.5 %) and 26 females (25.5 %). The age of most of the farmers was 53.4 ± 8.7 years. Out of 102, 21 farmers used carbamate pesticides. The results showed that the AChE and the BChE activity levels of all the farmers were 3.27 ± 0.84 Unit/mL and 2.15 ± 0.58 Unit/mL, respectively. The AChE and the BChE activity levels in males were 3.31 ± 0.88 Unit/mL and 1.97 ± 0.60 U/mL, respectively, during winter and 3.27 ± 0.82 Unit/mL and 2.15 ± 0.58 U/mL, respectively, during the hot season, and AChE and the BChE activity levels in females were 3.27 ± 0.82 U/mL and 2.44 ± 0.56 U/mL, respectively, during the hot season. The cholinesterase activity levels, both AChE and BChE, in the male farmers' blood had significant difference between the two seasons, while in the case of the female farmers, there was significant difference in the BChE activity levels, at p < 0.05. The BChE activity level was found to significantly correlate with self-spray (p < 0.05), which implies that the BChE activity decreased when they sprayed by themselves. The cholinesterase activity levels of the present study were lower than those of the other

Coamplification of human acetylcholinesterase and butyrylcholinesterase genes in blood cells: Correlation with various leukemias and abnormal megakaryocytopoiesis

International Nuclear Information System (INIS)

Lapidot-Lifson, Y.; Prody, C.A.; Ginzberg, D.; Meytes, D.; Zakut, H.; Soreq, H.

1989-01-01

To study the yet unknown role of the ubiquitous family of cholinesterases (ChoEases) in developing blood cells, the recently isolated cDNAs encoding human acetylcholinesterase and butyrylcholinesterase were used in blot hybridization with peripheral blood DNA from various leukemic patients. Hybridization signals and modified restriction patterns were observed with both cDNA probes in 4 of the 16 leukemia DNA preparations examined. These reflected the amplification of the corresponding AcCho-Ease and BtChoEase genes (ACHE and CHE) and alteration in their structure. Parallel analysis of 30 control samples revealed nonpolymorphic, much weaker hybridization signals for each of the probes. In view of previous reports on the effect of acetylcholine analogs and ChoEase inhibitors in the induction of megakaryocytopoiesis and production of platelets in the mouse. The authors further searched for such phenomena in nonleukemic patients with platelet production disorders. Amplifications of both ACHE and CHE genes were found in 2 of the 4 patients so far examined. Pronounced coamplification of these two related but distinct genes in correlation with pathological production of blood cells suggests a functional role for members of the ChoEase family in megakaryocytopoiesis and raises the question whether the coamplification of these genes could be casually involved in the etiology of hemocytopoietic disorders

New generic approach to the treatment of organophosphate poisoning: Adenosine receptor mediated inhibition of ACh-release

NARCIS (Netherlands)

Helden, H.P.M. van; Groen, B.; Moor, E.; Westerink, B.H.C.; Bruijnzeel, P.L.B.

1998-01-01

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

New generic approach to the treatment of organophosphate poisoning : Adenosine receptor mediated inhibition of ACh-release

NARCIS (Netherlands)

van Helden, HPM; Moor, E; Westerink, BHC; Bruijnzeel, PLB

1998-01-01

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

Syntheses and characterization of novel oxoisoaporphine derivatives as dual inhibitors for cholinesterases and amyloid beta aggregation.

Science.gov (United States)

Li, Yan-Ping; Ning, Fang-Xian; Yang, Meng-Bi; Li, Yong-Cheng; Nie, Min-Hua; Ou, Tian-Miao; Tan, Jia-Heng; Huang, Shi-Liang; Li, Ding; Gu, Lian-Quan; Huang, Zhi-Shu

2011-05-01

A series of 3-substituted (5c-5f, 6c-6f) and 4-substituted (10a-10g) oxoisoaporphine derivatives were synthesized. It was found that all these synthetic compounds had IC50 values at micro or nano molar range for cholinesterase inhibition, and most of them could inhibit amyloid β (Aβ) self-induced aggregation with inhibition ratio from 31.8% to 57.6%. The structure-activity relationship studies revealed that the derivatives with higher selectivity on AChE also showed better inhibition on Aβ self-induced aggregation. The results from cell toxicity study indicated that most quaternary methiodide salts had higher IC50 values than the corresponding non-quaternary compounds. This study provided potentially important information for further development of oxoisoaporphine derivatives as lead compounds for the treatment of Alzheimer's disease. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Synthesis and discovery of highly functionalized mono- and bis-spiro-pyrrolidines as potent cholinesterase enzyme inhibitors.

Science.gov (United States)

Kia, Yalda; Osman, Hasnah; Suresh Kumar, Raju; Basiri, Alireza; Murugaiyah, Vikneswaran

2014-04-01

Novel mono and bis spiropyrrolidine derivatives were synthesized via an efficient ionic liquid mediated, 1,3-dipolar cycloaddition methodology and evaluated in vitro for their AChE and BChE inhibitory activities in search for potent cholinesterase enzyme inhibitors. Most of the synthesized compounds displayed remarkable AChE inhibitory activities with IC50 values ranging from 1.68 to 21.85 μM, wherein compounds 8d and 8j were found to be most active inhibitors against AChE and BChE with IC50 values of 1.68 and 2.75 μM, respectively. Molecular modeling simulation on Torpedo californica AChE and human BChE receptors, showed good correlation between IC50 values and binding interaction template of the most active inhibitors docked into the active site of their relevant enzymes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

Energy Technology Data Exchange (ETDEWEB)

Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel; Chapman, Shira; Bloch-Shilderman, Eugenia; Grauer, Ettie, E-mail: ettieg@iibr.gov.il

2016-11-01

Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. In all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti-inflammatory intervention.

Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

International Nuclear Information System (INIS)

Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel; Chapman, Shira; Bloch-Shilderman, Eugenia; Grauer, Ettie

2016-01-01

Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. In all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti-inflammatory intervention.

Automatización del control del cálculo de extracciones en la mina de la empresa niquelera Ernesto Che Guevara

Directory of Open Access Journals (Sweden)

Arístides A. Legrá-Lobaina

2010-03-01

Full Text Available En el artículo se muestran los elementos fundamentales de un algoritmo cuyo objetivo es establecer el contenido y el orden de los procedimientos necesarios para realizar el control del cálculo de extracciones en la mina de la empresa Ernesto Che Guevara que explota, a cielo abierto, yacimientos lateríticos ferroniquelíferos en la región de Moa, Cuba. Asimismo se presenta el diseño de los diálogos informáticos que han automatizado el algoritmo en la aplicación informática Tierra.

Cholinesterase inhibitors in mild cognitive impairment: a systematic review of randomised trials.

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Roberto Raschetti

2007-11-01

Full Text Available Mild cognitive impairment (MCI refers to a transitional zone between normal ageing and dementia. Despite the uncertainty regarding the definition of MCI as a clinical entity, clinical trials have been conducted in the attempt to study the role of cholinesterase inhibitors (ChEIs currently approved for symptomatic treatment of mild to moderate Alzheimer disease (AD, in preventing progression from MCI to AD. The objective of this review is to assess the effects of ChEIs (donepezil, rivastigmine, and galantamine in delaying the conversion from MCI to Alzheimer disease or dementia.The terms "donepezil", "rivastigmine", "galantamine", and "mild cognitive impairment" and their variants, synonyms, and acronyms were used as search terms in four electronic databases (MEDLINE, EMBASE, Cochrane, PsycINFO and three registers: the Cochrane Collaboration Trial Register, Current Controlled Trials, and ClinicalTrials.gov. Published and unpublished studies were included if they were randomized clinical trials published (or described in English and conducted among persons who had received a diagnosis of MCI and/or abnormal memory function documented by a neuropsychological assessment. A standardized data extraction form was used. The reporting quality was assessed using the Jadad scale. Three published and five unpublished trials met the inclusion criteria (three on donepezil, two on rivastigmine, and three on galantamine. Enrolment criteria differed among the trials, so the study populations were not homogeneous. The duration of the trials ranged from 24 wk to 3 y. No significant differences emerged in the probability of conversion from MCI to AD or dementia between the treated groups and the placebo groups. The rate of conversion ranged from 13% (over 2 y to 25% (over 3 y among treated patients, and from 18% (over 2 y to 28% (over 3 y among those in the placebo groups. Only for two studies was it possible to derive point estimates of the relative risk of

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

Science.gov (United States)

Bautista-Aguilera, Oscar M; Esteban, Gerard; Chioua, Mourad; Nikolic, Katarina; Agbaba, Danica; Moraleda, Ignacio; Iriepa, Isabel; Soriano, Elena; Samadi, Abdelouahid; Unzeta, Mercedes; Marco-Contelles, José

2014-01-01

The design, synthesis, and biochemical evaluation of donepezil-pyridyl hybrids (DPHs) as multipotent cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors for the potential treatment of Alzheimer's disease (AD) is reported. The 3D-quantitative structure-activity relationship study was used to define 3D-pharmacophores for inhibition of MAO A/B, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) enzymes and to design DPHs as novel multi-target drug candidates with potential impact in the therapy of AD. DPH14 (Electrophorus electricus AChE [EeAChE]: half maximal inhibitory concentration [IC50] =1.1±0.3 nM; equine butyrylcholinesterase [eqBuChE]: IC50 =600±80 nM) was 318-fold more potent for the inhibition of AChE, and 1.3-fold less potent for the inhibition of BuChE than the reference compound ASS234. DPH14 is a potent human recombinant BuChE (hBuChE) inhibitor, in the same range as DPH12 or DPH16, but 13.1-fold less potent than DPH15 for the inhibition of human recombinant AChE (hAChE). Compared with donepezil, DPH14 is almost equipotent for the inhibition of hAChE, and 8.8-fold more potent for hBuChE. Concerning human monoamine oxidase (hMAO) A inhibition, only DPH9 and 5 proved active, compound DPH9 being the most potent (IC50 [MAO A] =5,700±2,100 nM). For hMAO B, only DPHs 13 and 14 were moderate inhibitors, and compound DPH14 was the most potent (IC50 [MAO B] =3,950±940 nM). Molecular modeling of inhibitor DPH14 within EeAChE showed a binding mode with an extended conformation, interacting simultaneously with both catalytic and peripheral sites of EeAChE thanks to a linker of appropriate length. Absortion, distribution, metabolism, excretion and toxicity analysis showed that structures lacking phenyl-substituent show better druglikeness profiles; in particular, DPHs13-15 showed the most suitable absortion, distribution, metabolism, excretion and toxicity properties. Novel donepezil-pyridyl hybrid DPH14 is a potent, moderately selective h

The influence of study species selection on estimates of pesticide exposure in free-ranging birds

Science.gov (United States)

Borges, Shannon L.; Vyas, Nimish B.; Christman, Mary C.

2014-01-01

Field studies of pesticide effects on birds often utilize indicator species with the purpose 16 of extrapolating to other avian taxa. Little guidance exists for choosing indicator species to 17 monitor the presence and/or effects of contaminants that are labile in the environment or body, 18 but are acutely toxic, such as anticholinesterase (anti-ChE) insecticides. Use of an indicator 19 species that does not represent maximum exposure and/or effects could lead to inaccurate risk 20 estimates. Our objective was to test the relevance of a priori selection of indicator species for a 21 study on pesticide exposure to birds inhabiting fruit orchards. We used total plasma 22 cholinesterase (ChE) activity and ChE reactivation to describe the variability in anti-ChE exposure among avian species in two conventionally managed fruit orchards. Of seven 24 species included in statistical analyses, the less common species, chipping sparrow (Spizella 25 passerina), showed the greatest percentage of exposed individuals and the greatest ChE 26 depression, whereas the two most common species, American robins (Turdus migratorius) and 27 grey catbirds (Dumatella carolinensis), did not show significant exposure. Due to their lower 28 abundance, chipping sparrows would have been an unlikely choice for study. Our results show 29 that selection of indicator species using traditionally accepted criteria such as abundance and 30 ease of collection may not identify species that are at greatest risk. Our efforts also demonstrate 31 the usefulness of conducting multiple-species pilot studies prior to initiating detailed studies on 32 pesticide effects. A study such as ours can help focus research and resources on study species 33 that are most appropriate.

Critical thresholds of liver function parameters for ketosis prediction in dairy cows using receiver operating characteristic (ROC) analysis.

Science.gov (United States)

Sun, Yuhang; Wang, Bo; Shu, Shi; Zhang, Hongyou; Xu, Chuang; Wu, Ling; Xia, Cheng

2015-01-01

Fatty liver syndrome and ketosis are important metabolic disorders in high-producing cows during early lactation with fatty liver usually preceding ketosis. To date, parameters for early prediction of the risk of ketosis have not been investigated in China. To determine the predictive value of some parameters on the risk of ketosis in China. In a descriptive study, 48 control and 32 ketotic Holstein Friesian cows were randomly selected from one farm with a serum β-hydroxybutyrate (BHBA) concentration of 1.20 mmol/L as cutoff point. The risk prediction thresholds for ketosis were determined by receiver operating characteristic (ROC) analysis. In line with a high BHBA concentration, blood glucose concentration was significantly lower in ketotic cows compared to control animals (2.77 ± 0.24 versus 3.34 ± 0.03 mmol/L; P = 0.02). Thresholds were more than 0.76 mmol/L for nonesterified fatty acids (NEFA, with 65% sensitivity and 92% specificity), more than 104 U/L for aspartate aminotransferase (AST, 74% and 85%, respectively), less than 140 U/L for cholinesterase (CHE, 75% and 59%, respectively), and more than 3.3 µmol/L for total bilirubin (TBIL, 58% and 83%, respectively). There were significant correlations between BHBA and glucose (R = -4.74), or CHE (R = -0.262), BHBA and NEFA (R = 0.520), or AST (R = 0.525), or TBIL (R = 0.278), or direct bilirubin (DBIL, R = 0.348). AST, CHE, TBIL and NEFA may be useful parameters for risk prediction of ketosis. This study might be of value in addressing novel directions for future research on the connection between ketosis and liver dysfunction.

Interactive toxicity of chlorpyrifos and parathion in neonatal rats: Role of esterases in exposure sequence-dependent toxicity

International Nuclear Information System (INIS)

Kacham, R.; Karanth, S.; Baireddy, P.; Liu, J.; Pope, C.

2006-01-01

We previously reported that sequence of exposure to chlorpyrifos and parathion in adult rats can markedly influence toxic outcome. In the present study, we evaluated the interactive toxicity of chlorpyrifos (8 mg/kg, po) and parathion (0.5 mg/kg, po) in neonatal (7 days old) rats. Rats were exposed to the insecticides either concurrently or sequentially (separated by 4 h) and sacrificed at 4, 8, and 24 h after the first exposure for biochemical measurements (cholinesterase activity in brain, plasma, and diaphragm and carboxylesterase activity in plasma and liver). The concurrently-exposed group showed more cumulative lethality (15/24) than either of the sequential dosing groups. With sequential dosing, rats treated initially with chlorpyrifos prior to parathion (C/P) exhibited higher lethality (7/23) compared to those treated with parathion before chlorpyrifos (P/C; 1/24). At 8 h after initial dosing, brain cholinesterase inhibition was significantly greater in the C/P group (59%) compared to the P/C group (28%). Diaphragm and plasma cholinesterase activity also followed a relatively similar pattern of inhibition. Carboxylesterase inhibition in plasma and liver was relatively similar among the treatment groups across time-points. Similar sequence-dependent differences in brain cholinesterase inhibition were also noted with lower binary exposures to chlorpyrifos (2 mg/kg) and parathion (0.35 mg/kg). In vitro and ex vivo studies compared relative oxon detoxification of carboxylesterases (calcium-insensitive) and A-esterases (calcium-sensitive) in liver homogenates from untreated and insecticide pretreated rats. Using tissues from untreated rats, carboxylesterases detoxified both chlorpyrifos oxon and paraoxon, while A-esterases only detoxified chlorpyrifos oxon. With parathion pretreatment, A-esterases still detoxified chlorpyrifos oxon while liver from chlorpyrifos pretreated rats had little apparent effect on paraoxon. We conclude that while neonatal rats are less

Organophosphate inhibition of avian salt gland Na, K-ATPase activity

Science.gov (United States)

Eastin, W.C.; Fleming, W.J.; Murray, H.C.

1982-01-01

1. Adult black ducks (Anas rubripes) were given freshwater or saltwater (1.5% NaCl) for 11 days and half of each group was also given an organophosphate (17 p.p.m. fenthion) in the diet on days 6–11.2. After 11 days, ducks drinking saltrwater had lost more weight and had higher plasma Na and uric acid concentration and osmolalities than birds drinking freshwater.3. Saltwater treatment stimulated the salt gland to increased weight and Na, K-ATPase activity.4. Fenthion generally reduced plasma and brain cholinesterase activity and depressed cholinesterase and Na, K-ATPase activities in salt glands of birds drinking saltwater.

SUSPECTED CARBARYL TOXICITY IN A CAPTIVE COLONY OF STRAW-COLORED FRUIT BATS ( EIDOLON HELVUM).

Science.gov (United States)

Selig, Michael; Lewandowski, Albert

2017-12-01

Carbaryl was the first carbamate insecticide produced and remains the most widely used due to its perceived low level of toxicity in nontarget species. This report describes the management and evaluation of a group of straw-colored fruit bats, Eidolon helvum, that were exposed to carbaryl. Cholinesterase activity of blood, retina, and brain was evaluated to further investigate whether carbaryl was the causative agent. Decreased whole blood and retinal cholinesterase activity coupled with the response to atropine suggests that the cause of the clinical signs in this bat colony was due to carbaryl exposure. Whole blood and retinal tissue may be the best samples for confirming carbamate exposure in this species.

Cholinesterase inhibitory activity and chemical constituents of Stenochlaena palustris fronds at two different stages of maturity

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Nelson Jeng-Yeou Chear

2016-04-01

Full Text Available Stenochlaena palustris fronds are popular as a vegetable in Southeast Asia. The objectives of this study were to evaluate the anticholinesterase properties and phytochemical profiles of the young and mature fronds of this plant. Both types of fronds were found to have selective inhibitory effect against butyrylcholinesterase compared with acetylcholinesterase. However, different sets of compounds were responsible for their activity. In young fronds, an antibutyrylcholinesterase effect was observed in the hexane extract, which was comprised of a variety of aliphatic hydrocarbons, fatty acids, and phytosterols. In the mature fronds, inhibitory activity was observed in the methanol extract, which contained a series of kaempferol glycosides. Our results provided novel information concerning the ability of S. palustris to inhibit cholinesterase and its phytochemical profile. Further research to investigate the potential use of this plant against Alzheimer's disease is warranted, however, young and mature fronds should be distinguished due to their phytochemical differences.

Preventive Role of Indian Black Pepper in Animal Models of Alzheimer’s Disease

Science.gov (United States)

Suresh, RN; MK, Jayanthi; HL, Kalabharathi; AM, Satish; VH, Pushpa

2015-01-01

Introduction: Dementia is the clinical symptom of alzheimer’s disease. Brain cholinesterase levels and behavioural changes are the markers for Alzheimer’s disease and aluminium chloride is one causative agent for polymerization of tau protein and amyloid plaque formation in Alzheimer’s disease. Effect of piper nigrum and its role in prevention of alzhimer’s disease and symptoms are well linked in this study. Aim: To study the effect of piper nigrum for the prevention of alzheimer’s associated histopathological, biochemical and behaviour changes in rat model. Materials and Methods: Twenty four rats were taken in this study. Their baseline behavioural parameters were noted and group was separated randomly in four. Rats were pretreated with piper nigrum and Alzheimer’s disease was induced. Biochemical and histopathological changes were noted at the end of experiment. Results: There was marked decrease in cholinesterase level, amyloidal plaque formation in rats brain who were pretreated with piper nigrum. At the same time there was decrease in escape latency time (ELT) and increase in memory in piper treated rats. Conclusion: Piper nigrum prove to be effective for prevention of Alzheimer’s disease. This finding has to be confirmed with studies including larger population. Further research on cholinesterase inhibitors, role of flavonoids on prevention of neurodegeneration in Alzheimer’s disease can be encouraged. PMID:26023568

Novel activation domain derived from Che-1 cofactor coupled with the artificial protein Jazz drives utrophin upregulation.

Science.gov (United States)

Desantis, Agata; Onori, Annalisa; Di Certo, Maria Grazia; Mattei, Elisabetta; Fanciulli, Maurizio; Passananti, Claudio; Corbi, Nicoletta

2009-02-01

Our aim is to upregulate the expression level of the dystrophin related gene utrophin in Duchenne muscular dystrophy, thus complementing the lack of dystrophin functions. To this end, we have engineered synthetic zinc finger based transcription factors. We have previously shown that the artificial three-zinc finger protein named Jazz fused with the Vp16 activation domain, is able to bind utrophin promoter A and to increase the endogenous level of utrophin in transgenic mice. Here, we report on an innovative artificial protein, named CJ7, that consists of Jazz DNA binding domain fused to a novel activation domain derived from the regulatory multivalent adaptor protein Che-1/AATF. This transcriptional activation domain is 100 amino acids in size and it is very powerful as compared to the Vp16 activation domain. We show that CJ7 protein efficiently promotes transcription and accumulation of the acetylated form of histone H3 on the genomic utrophin promoter locus.

Pharmacophore-based design and discovery of (-)-meptazinol carbamates as dual modulators of cholinesterase and amyloidogenesis.

Science.gov (United States)

Xie, Qiong; Zheng, Zhaoxi; Shao, Biyun; Fu, Wei; Xia, Zheng; Li, Wei; Sun, Jian; Zheng, Wei; Zhang, Weiwei; Sheng, Wei; Zhang, Qihong; Chen, Hongzhuan; Wang, Hao; Qiu, Zhuibai

2017-12-01

Multifunctional carbamate-type acetylcholinesterase (AChE) inhibitors with anti-amyloidogenic properties like phenserine are potential therapeutic agents for Alzheimer's disease (AD). We reported here the design of new carbamates using pharmacophore model strategy to modulate both cholinesterase and amyloidogenesis. A five-feature pharmacophore model was generated based on 25 carbamate-type training set compounds. (-)-Meptazinol carbamates that superimposed well upon the model were designed and synthesized, which exhibited nanomolar AChE inhibitory potency and good anti-amyloidogenic properties in in vitro test. The phenylcarbamate 43 was highly potent (IC 50 31.6 nM) and slightly selective for AChE, and showed low acute toxicity. In enzyme kinetics assay, 43 exhibited uncompetitive inhibition and reacted by pseudo-irreversible mechanism. 43 also showed amyloid-β (Aβ) lowering effects (51.9% decrease of Aβ 42 ) superior to phenserine (31% decrease of total Aβ) in SH-SY5Y-APP 695 cells at 50 µM. The dual actions of 43 on cholinergic and amyloidogenic pathways indicated potential uses as symptomatic and disease-modifying agents.

‘Unkind and cruel, to deceive your Son | In borrow’d Shapes, and his Embrace to shun’: Mother-son love in T. S. Eliot’s ‘La Figlia Che Piange’

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Matthew Geary

2015-01-01

Full Text Available T. S. Eliot's "La Figlia Che Piange" (1916 is a curious anomaly in his early works. It stands out as a love poem of outstanding grace portraying a more positive relationship to the feminine compared to other poems contemporaneous with its writing such as "The Love Song of St. Sebastian" (1914 and "Hysteria" (1915. This essay shows the import of Eliot's chosen epigraph for "La Figlia" taken from Virgil's Aeneid to have been largely neglected or misread by critics. As a consequence, it argues that critical readings have crucially missed the presence of a shrouded maternal aspect within the poem. Through the lens of Lacanian psychoanalysis and the work of adherents to Lacanian theory — such as Bruce Fink, Shoshana Felman and Slavoj Zizek — this paper newly argues that the poem's meditation on the issues of union and separation between two lovers is in fact a screen for deeper unconscious ambivalent feelings between mother and son. That is to say, Eliot's "La Figlia Che Piange" shows a failed attempt to reconstruct, traverse and separate from the "fundamental fantasy" unconsciously orientating the male speaker of the poem and his desire.

Biochemical and locomotor responses of Carcinus maenas exposed to the serotonin reuptake inhibitor fluoxetine.

Science.gov (United States)

Mesquita, Sofia Raquel; Guilhermino, Lúcia; Guimarães, Laura

2011-10-01

The aim of this study was to assess the effects of the widely used anti-depressant fluoxetine on behaviour (locomotion), moulting, neuromuscular transmission, energy production and anti-oxidant defences' efficiency of the epibenthic crab Carcinus maenas. Crabs were individually exposed to fluoxetine concentrations for 7d. Effects on locomotion were assessed at the end of the exposure using an open field test adapted to C. maenas in the present study. Tissue samples were later collected to evaluate fluoxetine effects on physiological functions using the activity of key enzymes and other parameters as biomarkers, namely: N-acetyl-β-glucosaminidase (NAGase) in the epidermis (moulting) and the hepatopancreas; cholinesterases (ChE) in muscle (neuromuscular cholinergic transmission); NADP(+)-dependent isocitrate dehydrogenase (IDH) and lactate dehydrogenease (LDH) in muscle (energy production); glutathione S-transferases (GST) in hepatopancreas (biotransformation and oxidative stress system); glutathione reductase (GR), and glutathione peroxidade (GPx), total glutathione levels (TG) and lipid peroxidation levels in the hepatopancreas (anti-oxidant defences and oxidative damage). Because no information on C. maenas NAGase activity was previously available, its variation during the moult cycle was also investigated. The results showed that locomotion was significantly increased at fluoxetine concentrations equal or above 120 μg L⁻¹, with animals spending more time moving, walking longer distances than controls. Levels of NAGase activity were found to vary in relation to C. maenas moult cycle, but no alterations were observed after exposure to fluoxetine. Significant increases in the activity of ChE, GST and GR enzymes, and the levels of TG were found, with a lowest observed effect concentration (LOEC) of 120 μg L⁻¹. Effects on locomotion were significantly and positively correlated to those induced on ChE activity. The results raise concern when hypothesising

Identification of a novel alternative splicing variant of hemocyanin from shrimp Litopenaeus vannamei.

Science.gov (United States)

Zhao, Shan; Lu, Xin; Zhang, Yueling; Zhao, Xianliang; Zhong, Mingqi; Li, Shengkang; Lun, Jingsheng

2013-01-01

Recent evidences suggest that invertebrates express families of immune molecules with high levels of sequence diversity. Hemocyanin is an important non-specific immune molecule present in the hemolymph of both mollusks and arthropods. In the present study, we characterized a novel alternative splicing variant of hemocyanin (cHE1) from Litopenaeus vannamei that produced mRNA transcript of 2579 bp in length. The isoform contained two additional sequences of 296 and 267 bp in the 5'- and 3'-terminus respectively, in comparison to that of wild type hemocyanin (cHE). Sequence of cHE1 shows 100% identity to that of hemocyanin genomic DNA (HE, which does not form an open reading frame), suggesting that cHE1 might be an alternative splicing variant due to intron retention. Moreover, cHE1 could be detected by RT-PCR from five tissues (heart, gill, stomach, intestine and brain), and from shrimps at stages from nauplius to mysis larva. Further, cHE1 mRNA transcripts were significantly increased in hearts after 12h of infection with Vibrio parahemolyticus or poly I: C, while no significant difference in the transcript levels of hepatopancreas cHE was detected in the pathogen-treated shrimps during the period. In summary, these studies suggested a novel splicing variant of hemocyanin in shrimp, which might be involved in shrimp resistance to pathogenic infection. Copyright © 2013 Elsevier B.V. All rights reserved.

Phosalone-Induced Changes in Regional Cholinesterase Activities ...

African Journals Online (AJOL)

Nekky Umera

Male albino rats were given a daily oral dose of phosalone (41.35 mg, equivalent to ¼ of ... dislocation and the brain areas, viz. the cerebral cortex (CT), cerebellum .... AChE in CB and HP is interesting as these areas are associated with motor.

Conditions of concentration and composition of suspended load in the Vistula River between Wyszogród and Chełmno

Science.gov (United States)

Kaszubski, Michal

2014-05-01

The main objective of the study is to explain causes of variations of concentration, particle size distribution and composition of suspended load in the riverbed of the lower Vistula between Wyszogród and Chełmno. The study was conducted in seven bridge cross-sections (three above and four below the Włocławek reservoir). In each cross-section, three water samples were collected in the characteristic parts of the riverbed. Since July 2012 fifteen measurement series were carried out. During each measurement series 22 samples of water were collected. In each sample the overall concentration of suspended load, the proportion of the organic matter and particle size distribution of the mineral fraction were measured. Variation of concentration and characteristics of suspended load were studied both in the cross-sections of the Vistula riverbed and along its longitudinal profile. The study focus primarily on determining the qualitative and quantitative variation in the properties of suspended load in the cross-sections located in different morphological riverbed type, various level of its hydrotechnical management, including the operation on the Włocławek reservoir, and the diversity of the water flow conditions. The author tested the correlation occurring between the size of suspended load concentration as well as the flow rate and flow velocity at the water sampling sites. Moreover, the author determined the effect of morphological variation of the Vistula riverbed (the riverbed depth and the location of points of collecting water samples relative to the riverbed mesoforms) on the concentration size, composition structure and the particle size distribution of suspended load. Measurement sessions were chosen in such a way as to cover the widest possible spectrum of the water flow conditions in the riverbed of the Vistula. In addition to the low and medium flow the variability in concentration during flood flows of various types (ice jam, snowmelt and rainfall) were

Pharmacological evidences for antiamnesic potentials of ...

African Journals Online (AJOL)

Phyllanhus amarus (PAs) is commonly known as Bhumi amla and is traditionally used since centuries in ayurveda. The present study was undertaken to investigate the effects of PAs on cognitive functions and brain cholinesterase activity in mice. PAs (50, 100 and 200 mg/kg) produced a dose- dependent improvement in ...

La spirale dell’azzardo: una subcultura del gioco che “evapora” le relazioni / La spirale du jeu de hasard : une sous-culture qui empêche toute relation / The gambling: a subculture of game that “burns” the relationships

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Molin Valentina

2011-07-01

Full Text Available In this paper I have analysed the characteristics of what I define the “gambling subculture”, which is detectable in certain gaming environments and in subgroups of particularly “rabid” players. Within these subcultures there have been identified rules and sanctions, values, consolidate behaviours, characterization of relationships and interactions, and the conclusion is that what is built within the gambling environment is a separate universe, an “outer reality”, in which the values of the world “outside” change. It was also possible to conclude that, to join the gambling world for a gambler – learning its rules, sharing its values, developing relations inside it – represents a stimulus for gambling habits, as it allows to consider as “normal” their behaviour thanks to positive feedback from their groups of fellow players, and to the neutralization of possible negative feedback from “non-players”.Nel presente contributo vengono analizzate le caratteristiche di quella che ho definito “subcultura dell'azzardo”, rilevabile in determinati ambienti ludici e in sotto-gruppi di giocatori particolarmente “accaniti”. Di queste forme di subcultura sono state individuate norme e sanzioni, valori, comportamenti consolidati, caratterizzazione delle relazioni e delle interazioni, giungendo alla conclusione che quello che viene costruito negli spazi di gioco rappresenta un universo separato, un “extraluogo”, nel quale vengono scritte nuove regole e nel quale cambiano i valori rispetto al mondo “esterno”. È stato possibile inoltre concludere che l'adesione all'“universo gioco” – l'interiorizzazione delle sue norme, la condivisione dei suoi valori, lo sviluppo di relazioni al suo interno – rappresenta un fattore di mantenimento della condotta ludica, poiché permette di considerare “normale” il proprio comportamento grazie ai rinforzi positivi che giungono dal gruppo dei compagni-giocatori e alla

The effect of diminazene aceturate on cholinesterase activity in dogs with canine babesiosis

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R.J. Milner

1997-07-01

Full Text Available A clinical trial was designed to evaluate the effects of diminazene aceturate and its stabiliser antipyrine on serum pseudocholinesterase (PChE and red blood cell acetylcholinesterase (RBC AChE in dogs with babesiosis. The trial was conducted on naturally occurring, uncomplicated cases of babesiosis (n = 20 that were randomly allocated to groups receiving a standard therapeutic dose of diminazene aceturate with antipyrine stabiliser (n = 10 or antipyrine alone (n = 10. Blood was drawn immediately before and every 15 minutes for 1 hour after treatment. Plasma PChE showed a 4 % decrease between 0 and 60 min within the treatment group (p < 0.05. No statistically significant differences were found between the treatment and control groups at any of the time intervals for PChE. There was an increase in RBC AChE activity at 15 min in the treatment group (p < 0.05. No significant differences were found between the treatment and control groups at any time interval for RBC AChE. In view of the difference in PChE, samples from additional, new cases (n = 10 of canine babesiosis were collected to identify the affect of the drug over 12 hours. No significant depression was identified over this time interval. The results suggests that the underlying mechanism in producing side-effects, when they do occur, is unlikely to be through cholinesterase depression.

The Antioxidant Additive Approach for Alzheimer's Disease Therapy: New Ferulic (Lipoic) Acid Plus Melatonin Modified Tacrines as Cholinesterases Inhibitors, Direct Antioxidants, and Nuclear Factor (Erythroid-Derived 2)-Like 2 Activators.

Science.gov (United States)

Benchekroun, Mohamed; Romero, Alejandro; Egea, Javier; León, Rafael; Michalska, Patrycja; Buendía, Izaskun; Jimeno, María Luisa; Jun, Daniel; Janockova, Jana; Sepsova, Vendula; Soukup, Ondrej; Bautista-Aguilera, Oscar M; Refouvelet, Bernard; Ouari, Olivier; Marco-Contelles, José; Ismaili, Lhassane

2016-11-10

Novel multifunctional tacrines for Alzheimer's disease were obtained by Ugi-reaction between ferulic (or lipoic acid), a melatonin-like isocyanide, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order to modulate the oxidative stress as therapeutic strategy. Compound 5c has been identified as a promising permeable agent showing excellent antioxidant properties, strong cholinesterase inhibitory activity, less hepatotoxicity than tacrine, and the best neuroprotective capacity, being able to significantly activate the Nrf2 transcriptional pathway.

UHPLC-ESI-ORBITRAP-MS analysis of the native Mapuche medicinal plant palo negro (Leptocarpha rivularis DC. - Asteraceae) and evaluation of its antioxidant and cholinesterase inhibitory properties.

Science.gov (United States)

Jiménez-González, Andrea; Quispe, Cristina; Bórquez, Jorge; Sepúlveda, Beatriz; Riveros, Felipe; Areche, Carlos; Nagles, Edgar; García-Beltrán, Olimpo; Simirgiotis, Mario J

2018-12-01

UHPLC/ESI/MS identification of organic compounds is the first step in the majority of screening techniques for the characterization of biologically active metabolites in natural sources. This paper describes a method for the fast identification and characterisation of secondary metabolites in Leptocarpha rivularis DC. (Palo negro) extracts by HPLC/UV (DAD)-Mass Spectrometry (HPLC/MS). The plant is used for the treatment of several diseases since pre-hispanic Mapuche times. Thirty-seven compounds were detected in the aqueous edible extract for the first time including 4 sesquiterpenes, 10 flavonoids, 9 oxylipins, 2 organic acids, and 11 phenolic acids. In addition, phenolic content antioxidant and cholinesterase inhibitory activities were measured for the first time using the edible infusion. The total polyphenol content of the infusion was 230.76 ± 2.5 mmol GAE/kg dry weight, while the antioxidant activity was 176.51 ± 28.84; 195.28 ± 4.83; and 223.92 ± 2.95 mmol TE/kg dry weight, for the DPPH, ABTS, and FRAP assays, respectively. The cholinesterase inhibitory activity was 7.38 ± 0.03 and 5.74 ± 0.06 mmol GALAE/kg, for the inhibition of acetylcholinesterase AChE and BChE, respectively, showing that this plant is a candidate for the isolation of compounds that can be useful for the treatment of neurodegenerative diseases. Furthermore, this plant could serve also as a raw material for the production of dietary supplements, due to its content of polyphenolic compounds.

Transthyretin as a potential CSF biomarker for Alzheimer's disease and dementia with Lewy bodies: effects of treatment with cholinesterase inhibitors

DEFF Research Database (Denmark)

Schultz, K; Nilsson, K; Nielsen, Jørgen Erik

2010-01-01

BACKGROUND: Previous studies have indicated that transthyretin (TTR) levels in cerebrospinal fluid (CSF) are altered in depression and dementia. The present study aimed to investigate whether CSF TTR can be used to discriminate between patients with Alzheimer's disease (AD) and patients...... with dementia with Lewy bodies (DLB) with or without medication, as well as to reveal whether CSF TTR correlates with depression in dementia. METHODS: CSF samples from 59 patients with AD, 13 patients with DLB and 13 healthy controls were collected, and biochemical analysis was performed. Subjects were assessed...... for the presence of depression. RESULTS: No significant differences in CSF TTR were found between AD, DLB, and control subjects or between depressed and non-depressed dementia patients. Interestingly, we found a significant reduction in CSF TTR (14%) in AD patients who were medicated with cholinesterase inhibitors...

Correlación y conversión entre los valores de actividad de la colinesterasa plasmática medida por tres técnicas diferentes Correlation and conversion of plasma cholinesterase activity values using three techniques

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Jaime Carmona-Fonseca

2007-07-01

Full Text Available OBJETIVO: Determinar las relaciones matemáticas entre tres técnicas cuantitativas empleadas para medir la actividad de la colinesterasa plasmática, a partir de los valores de referencia ya establecidos para dos poblaciones de Antioquia, Colombia. MÉTODOS:Diseño descriptivo, transversal y prospectivo. Se conformaron dos muestras independientes representativas de la población laboral adulta (18-65 años, no expuesta a plaguicidas inhibidores de la colinesterasa y vinculada al Seguro Social, del valle de Aburrá (415 personas y del cercano oriente antioqueño (412 personas, del departamento de Antioquia, Colombia. La colinesterasa plasmática (EC 3.1.1.8 se midió mediante tres técnicas cuantitativas: Michel, EQM® y Monotest®. Se elaboraron ecuaciones de regresión que relacionaran entre sí los resultados de las tres técnicas estudiadas. RESULTADOS: Se definieron seis ecuaciones de regresión lineal simple que permitieron relacionar los resultados de las tres técnicas de medición de colinesterasa plasmática analizadas. La correlación entre las técnicas fue moderada (r: de 0,686 a 0,771, pero aumentó (r: de 0,744 a 0,811 al eliminar 12 (1,5% valores extremos. Las asociaciones entre las técnicas fueron altamente significativas (P OBJECTIVES: To determine mathematical correlations of three quantitative techniques to measure plasma cholinesterase, using reference values already established for two populations in the department of Antioquia, Colombia. METHODS: In this descriptive, cross-sectional, prospective study, two independent, representative samples of working adults (18 to 65 years old were examined. In both samples the adults worked for businesses associated with Colombia’s Social Security system. Adults in the two samples had not been exposed to cholinesterase-inhibiting pesticides. The samples were from two neighboring regions of the department of Antioquia: one sample (415 adults was from the Aburrá Valley, and the other

Characterization of acetylcholinesterase-inhibition by itopride.

Science.gov (United States)

Iwanaga, Y; Kimura, T; Miyashita, N; Morikawa, K; Nagata, O; Itoh, Z; Kondo, Y

1994-11-01

Itopride is a gastroprokinetic benzamide derivative. This agent inhibited both electric eel acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BuChE). The IC50 of itopride with AChE (2.04 +/- 0.27 microM) was, however, 100-fold less than that with BuChE, whereas in the case of neostigmine with AChE (11.3 +/- 3.4 nM), it was 10-fold less. The recovery of AChE activity inhibited by 10(-7) M neostigmine was partial, but that inhibited by up to 3 x 10(-5) M itopride was complete when the reaction mixture was subjected to ultrafiltration. Double reciprocal plots of the experimental data showed that both Km and Vmax were affected by itopride, suggesting that the inhibition is a "mixed" type, although primarily being an uncompetitive one. The inhibitory effect of itopride on cholinesterase (ChE) activity in guinea pig gastrointestine was much weaker than that on pure AChE. However, in the presence of a low dose of diisopropyl fluorophosphate, just enough to inhibit BuChE but not AChE, the IC50s of itopride against ChE activities were found to be about 0.5 microM. In conclusion, itopride exerts reversible and a "mixed" type of inhibition preferably against AChE. The IC50 of itopride for electric eel and guinea pig gastrointestinal AChE inhibition was 200 times and 50 times as large as that of neostigmine, respectively.

Reconocimiento Mapu-Che de Chile: Tratado ante Constitución, Historia frente a Derecho

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Bartolomé CLAVERO SALVADOR

2011-04-01

Full Text Available Desde el año 1991, el compromiso adquirido por los sucesivos gobiernos chilenos para reconocer a nivel constitucional la presencia indígena en el ordenamiento del Estado ha puesto de manifiesto el desconocimiento académico y jurídico mutuo por parte de Chile con respecto a las evidencias para una reposición de Mapu-Che. El presente trabajo hace un recorrido histórico y jurídico por las formas de relación entre el Estado chileno y el Estado Mapu, que hasta la conquista chilena de Mapu en la década de los ochenta del siglo XIX se manifestaron a través de Tratados y Parlamentos que implicaban un reconocimiento mutuo de ambas entidades en una esfera internacional. Las comisiones de estudios, informes oficiales e invocaciones de verdad para un nuevo trato, primero de las Naciones Unidas, y después de la República de Chile, han observado estas evidencias de la significación constitucional e internacional de los Tratados, pero Chile ha convertido su peculiar forma de reconocimiento constitucional de la presencia indígena en un alarde de unidad e indivisibilidad nacional. Este encubrimiento nace del deseo de mantener una Constitución exclusiva, al que se une la certeza de que otra forma de reconocimiento obligaría a un replanteamiento de las propias raíces de los fundamentos constitucionales de la República de Chile.

Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent deet

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Dimitrov Mitko

2009-08-01

Full Text Available Abstract Background N,N-Diethyl-3-methylbenzamide (deet remains the gold standard for insect repellents. About 200 million people use it every year and over 8 billion doses have been applied over the past 50 years. Despite the widespread and increased interest in the use of deet in public health programmes, controversies remain concerning both the identification of its target sites at the olfactory system and its mechanism of toxicity in insects, mammals and humans. Here, we investigated the molecular target site for deet and the consequences of its interactions with carbamate insecticides on the cholinergic system. Results By using toxicological, biochemical and electrophysiological techniques, we show that deet is not simply a behaviour-modifying chemical but that it also inhibits cholinesterase activity, in both insect and mammalian neuronal preparations. Deet is commonly used in combination with insecticides and we show that deet has the capacity to strengthen the toxicity of carbamates, a class of insecticides known to block acetylcholinesterase. Conclusion These findings question the safety of deet, particularly in combination with other chemicals, and they highlight the importance of a multidisciplinary approach to the development of safer insect repellents for use in public health.

Novel Cholinesterase Inhibitors Based on O-Aromatic N,N-Disubstituted Carbamates and Thiocarbamates

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Martin Krátký

2016-02-01

Full Text Available Based on the presence of carbamoyl moiety, twenty salicylanilide N,N-disubstituted (thiocarbamates were investigated using Ellman’s method for their ability to inhibit acetylcholinesterase (AChE and butyrylcholinesterase (BChE. O-Aromatic (thiocarbamates exhibited weak to moderate inhibition of both cholinesterases with IC50 values within the range of 1.60 to 311.0 µM. IC50 values for BChE were mostly lower than those obtained for AChE; four derivatives showed distinct selectivity for BChE. All of the (thiocarbamates produced a stronger inhibition of AChE than rivastigmine, and five of them inhibited BChE more effectively than both established drugs rivastigmine and galantamine. In general, 5-chloro-2-hydroxy-N-[4-(trifluoromethyl-phenyl]benzamide, 2-hydroxy-N-phenylbenzamide as well as N-methyl-N-phenyl carbamate derivatives led to the more potent inhibition. O-{4-Chloro-2-[(4-chlorophenylcarbamoyl]phenyl} dimethylcarbamothioate was identified as the most effective AChE inhibitor (IC50 = 38.98 µM, while 2-(phenylcarbamoylphenyl diphenylcarbamate produced the lowest IC50 value for BChE (1.60 µM. Results from molecular docking studies suggest that carbamate compounds, especially N,N-diphenyl substituted representatives with considerable portion of aromatic moieties may work as non-covalent inhibitors displaying many interactions at peripheral anionic sites of both enzymes. Mild cytotoxicity for HepG2 cells and consequent satisfactory calculated selectivity indexes qualify several derivatives for further optimization.

Chemical Composition of Volatiles; Antimicrobial, Antioxidant and Cholinesterase Inhibitory Activity of Chaerophyllum aromaticum L. (Apiaceae) Essential Oils and Extracts.

Science.gov (United States)

Petrović, Goran M; Stamenković, Jelena G; Kostevski, Ivana R; Stojanović, Gordana S; Mitić, Violeta D; Zlatković, Bojan K

2017-05-01

The present study reports the chemical composition of the headspace volatiles (HS) and essential oils obtained from fresh Chaerophyllum aromaticum root and aerial parts in full vegetative phase, as well as biological activities of their essential oils and MeOH extracts. In HS samples, the most dominant components were monoterpene hydrocarbons. On the other hand, the essential oils consisted mainly of sesquiterpenoids, representing 73.4% of the root and 63.4% of the aerial parts essential oil. The results of antibacterial assay showed that the aerial parts essential oil and MeOH extract have no antibacterial activity, while the root essential oil and extract showed some activity. Both of the tested essential oils exhibited anticholinesterase activity (47.65% and 50.88%, respectively); MeOH extract of the root showed only 8.40% inhibition, while aerial part extract acted as an activator of cholinesterase. Regarding the antioxidant activity, extracts were found to be more effective than the essential oils. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Butyryl- and acetyl-cholinesterase inhibitory activities in essential oils of Salvia species and their constituents.

Science.gov (United States)

Savelev, Sergey U; Okello, Edward J; Perry, Elaine K

2004-04-01

Extracts of Salvia (sage) species have been reported to have cholinergic activities relevant to the treatment of Alzheimer's disease. A lack of information on the inhibition of the enzyme butyrylcholinesterase, also considered to be a target in the treatment of the disease, prompted this in vitro investigation of the essential oils of S. fruticosa, S. lavandulaefolia, S. of ficinalis and S. of ficinalis var. purpurea for anti-butyrylcholinesterase activity. Dose-dependent inhibition of human cholinesterases by the extracts and constituents was determined using the method of Ellman. A time dependent increase in the inhibition of butyrylcholinesterase by the oils of S. fruticosa and S. of ficinalis var. purpurea was evident. IC(50) values decreased from 0.15 +/- 0.007 and 0.14 +/- 0.007 mg/mL after 5 min to 0.035 +/- 0.016 and 0.06 +/- 0.018 mg/mL after 90 min incubation time respectively. The slow onset of inhibition of butyrylcholinesterase was also shown by individual constituents, such as 3-carene and beta-pinene. Analyses of the chemical composition of the oils and anti-butyrylcholinesterase activity of their constituents revealed that none of the compounds tested would account for the total activity of the oils and that synergy is likely. Copyright 2004 John Wiley & Sons, Ltd.

Disease-modifying anti-Alzheimer's drugs: inhibitors of human cholinesterases interfering with β-amyloid aggregation.

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Brogi, Simone; Butini, Stefania; Maramai, Samuele; Colombo, Raffaella; Verga, Laura; Lanni, Cristina; De Lorenzi, Ersilia; Lamponi, Stefania; Andreassi, Marco; Bartolini, Manuela; Andrisano, Vincenza; Novellino, Ettore; Campiani, Giuseppe; Brindisi, Margherita; Gemma, Sandra

2014-07-01

We recently described multifunctional tools (2a-c) as potent inhibitors of human Cholinesterases (ChEs) also able to modulate events correlated with Aβ aggregation. We herein propose a thorough biological and computational analysis aiming at understanding their mechanism of action at the molecular level. We determined the inhibitory potency of 2a-c on Aβ1-42 self-aggregation, the interference of 2a with the toxic Aβ oligomeric species and with the postaggregation states by capillary electrophoresis analysis and transmission electron microscopy. The modulation of Aβ toxicity was assessed for 2a and 2b on human neuroblastoma cells. The key interactions of 2a with Aβ and with the Aβ-preformed fibrils were computationally analyzed. 2a-c toxicity profile was also assessed (human hepatocytes and mouse fibroblasts). Our prototypical pluripotent analogue 2a interferes with Aβ oligomerization process thus reducing Aβ oligomers-mediated toxicity in human neuroblastoma cells. 2a also disrupts preformed fibrils. Computational studies highlighted the bases governing the diversified activities of 2a. Converging analytical, biological, and in silico data explained the mechanism of action of 2a on Aβ1-42 oligomers formation and against Aβ-preformed fibrils. This evidence, combined with toxicity data, will orient the future design of safer analogues. © 2014 John Wiley & Sons Ltd.

O-Hydroxyl- or o-amino benzylamine-tacrine hybrids: multifunctional biometals chelators, antioxidants, and inhibitors of cholinesterase activity and amyloid-β aggregation.

Science.gov (United States)

Mao, Fei; Huang, Ling; Luo, Zonghua; Liu, Anqiu; Lu, Chuanjun; Xie, Zhiyong; Li, Xingshu

2012-10-01

In an effort to identify novel multifunctional drug candidates for the treatment of Alzheimer's disease (AD), a series of hybrid molecules were synthesised by reacting N-(aminoalkyl)tacrine with salicylic aldehyde or derivatives of 2-aminobenzaldehyde. These compounds were then evaluated as multifunctional anti-Alzheimer's disease agents. All of the hybrids are potential biometal chelators, and in addition, most of them were better antioxidants and inhibitors of cholinesterases and amyloid-β (Aβ) aggregation than the lead compound tacrine. Compound 7c has the potential to be a candidate for AD therapy: it is a much better inhibitor of acetylcholinesterase (AChE) than tacrine (IC(50): 0.55 nM vs 109 nM), has good biometal chelation ability, is able to inhibit Aβ aggregation and has moderate antioxidant activity (1.22 Trolox equivalents). Copyright © 2012 Elsevier Ltd. All rights reserved.

Dual functional cholinesterase and MAO inhibitors for the treatment of Alzheimer's disease: synthesis, pharmacological analysis and molecular modeling of homoisoflavonoid derivatives.

Science.gov (United States)

Wang, Yali; Sun, Yang; Guo, Yueyan; Wang, Zechen; Huang, Ling; Li, Xingshu

2016-01-01

Because of the complexity of Alzheimer's disease (AD), the multi-target-directed ligand (MTDL) strategy is expected to provide superior effects for the treatment of AD, instead of the classic one-drug-one-target strategy. In this context, we focused on the design, synthesis and evaluation of homoisoflavonoid derivatives as dual acetyl cholinesterase (AChE) and monoamine oxidase (MAO-B) inhibitors. Among all the synthesized compounds, compound 10 provided a desired balance of AChE and hMAO-B inhibition activities, with IC50 value of 3.94 and 3.44 μM, respectively. Further studies revealed that compound 10 was a mixed-type inhibitor of AChE and an irreversible inhibitor of hMAO-B, which was also confirmed by molecular modeling studies. Taken together, the data indicated that 10 was a promising dual functional agent for the treatment of AD.

Fonofos poisons raptors and waterfowl several months after granular application.

Science.gov (United States)

Elliott, John E; Birmingham, Anna L; Wilson, Laurie K; McAdie, Malcolm; Trudeau, Suzanne; Mineau, Pierre

2008-02-01

From 1994 to 1999 in the Lower Fraser Valley region of southwest Canada, fonofos (Dyfonate G) was recommended for control of introduced wireworm (Agriotes spp.) pests on potato and other root crops. As part of a wildlife-monitoring program, we collected 15 raptors, including 12 bald eagles (Haliaeetus leucocephalus), found dead or debilitated on or near agricultural lands with severely inhibited brain and/or plasma cholinesterase activity and fonofos residues in ingesta. Bird remains, in nine cases waterfowl, were identified in the ingesta samples. Another seven bald eagles had severe cholinesterase inhibition, but without evidence of fonofos residues. During two winters from 1996 to 1998, 420 ha of potato fields, half of which had been treated the previous spring with fonofos and the remainder untreated, were searched weekly for evidence of wildlife mortality. Search efficiency was assessed with placed duck carcasses. Waterfowl outnumbered other species in field-use counts and comprised the greatest proportion of birds found dead. We found 211 wildlife remains, most scavenged; 35 intact carcasses were suitable for postmortem examination and/or toxicology analyses. Cholinesterase activity was assayed in brains of 18 waterfowl, five of which had severely depressed activity (average inhibition 74%; range, 69-78%). The gastrointestinal tract of a mallard found in a field treated with granular product contained 49 microg/g fonofos residues, linking waterfowl mortality with labelled use of the product. These findings demonstrate the risk of both primary and secondary poisoning by anticholinesterase insecticides where wildlife make intensive use of farmed fields.

Effects of acute and repeated oral exposure to the organophosphate insecticide chlorpyrifos on open-field activity in chicks.

Science.gov (United States)

Al-Badrany, Y M A; Mohammad, F K

2007-11-01

The effects of the organophosphate insecticide chlorpyrifos on 5min open-field activity were examined in a 7-15 days old chick model. Chlorpyrifos was acutely administered taking into account cholinesterase inhibition and determination of the acute (24h) median lethal dose (LD50). The oral LD50 value of chlorpyrifos in chicks was 18.14mg/kg, with cholinergic toxicosis observed on intoxicated chicks. Chlorpyrifos at the dose rates of 5,10 and 20mg/kg orally produced within 2h signs of cholinergic toxicosis in the chicks and significantly inhibited plasma (40-70%), whole brain (43-69%) and liver (31-46%) cholinesterase activities in a dose-dependent manner. Chlorpyrifos at 2 and 4mg/kg, orally did not produce overt signs of cholinergic toxicosis, but decreased (30, 60 and 90min after dosing) the general locomotor activity of the chicks as seen by a significant increase in the latency to move from the central square of the open-field arena, decreases in the numbers of lines crossed and vocalization score. Repeated daily chlorpyrifos treatments (2 and 4mg/kg, orally) for seven consecutive days also caused hypoactivity in chicks in the open-field behavioral paradigm. Only the high dose of chlorpyrifos (4mg/kg, orally) given repeatedly for 7 days caused significant cholinesterase inhibition in the whole brain (37%) and the liver (22%). In conclusion, chlorpyrifos at single or short-term repeated doses-induced behavioral changes in 7-15 days old chicks, in a model that could be used for further neurobehavioral studies involving subtle effects of organophosphates on chicks.

Sources of exposure to and public health implications of organophosphate pesticides

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Kushik Jaga

2003-09-01

Full Text Available OBJECTIVE: To review the public health significance of organophosphate pesticide exposure in the United States of America. Since the situation of high organophosphate pesticide exposure and the concomitant health risks in the developing countries of the world is well known, this article seeks to highlight the public health significance of organophosphate exposure in the United States, where it is less common than in many other nations. Looking at the situation in the United States would serve to further emphasize the seriousness of organophosphate pesticide-related health issues in developing countries. METHODS: A search for journal articles on organophosphate pesticides and organophosphate exposure was done on the PubMed electronic bibliographic database system of the National Library of Medicine of the United States. To supplement that search, information on organophosphate toxicity, biological monitoring, and regulation of pesticides was obtained from other published articles, textbooks, and relevant Internet sites. RESULTS: Organophosphate pesticides are a group of chemicals that are mainly used in agriculture. Organophosphates inhibit the activity of both the cholinesterase (ChE enzymes-red blood cell (RBC ChE and serum ChE-resulting in the cholinergic features of organophosphate toxicity. A 50% reduction in serum ChE activity from the baseline is an indication of acute organophosphate toxicity. The RBC ChE activity, which is less rapidly depressed than the serum ChE activity, is a measure of chronic exposure to organophosphates. Exposures to organophosphates are broadly classified into two categories: occupational and environmental. Occupational exposures occur among agricultural workers (including migrant farmworkers, industrial workers, pest control exterminators, and other workers. Nonoccupational exposure affects a large segment of the general population in the United States. Residential exposures come from organophosphate pesticide

RELÉ ELECTRÓNICO PARA LA DETECCIÓN DEL MOVIMIENTO EN LOS TANQUES DE SEDIMENTACIÓN DE LA EMPRESA COMANDANTE ¨ERNESTO CHE GUEVARA¨

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Orlys Ernesto Torres Breffe

2011-02-01

Full Text Available En este trabajo se muestran los resultados del diseño de un dispositivo electrónico para detectar el movimiento del tanquede sedimentación de la planta de lixiviación de la Empresa Ernesto Che Guevara.Estos tanque actualmente se encuentran sin esta protección y su parada por avería solo es detectada de forma visual por eloperario o cuando la densidad de la pulpa aumente a valores tan altos que sea reflejado en el sistema de monitoreo instalado(EROS. La parada inadvertida de estos tanque casi siempre sucede por razones fácilmente corregibles, pero si no se detectaa tiempo la sedimentación del minerales es casi inevitable y las pérdidas de recursos y materiales son cuantiosas.La propuesta electrónica en sustitución a las desechas electromagnéticas, es muy barata y su reproducción es fácilmenterealizable en la propia empresa, dado que los elementos que se utiliza son clásicos, sin exigencias de fabricación, tolerancias,etc.  The main goal of this research paper is to show the electronic device design results while dealing with the location of thesedimentation tank on the leaching plant located on Ernesto Che Guevara factory.Nowadays there is no protection for this tank, thus, if it stops working it can only be noticed by the engine sunner on avisual way or when the extremely high figures of the pulp density are reflected on the available monitor system (EROS.The unnoticed misfunctioning of this device is caused mainly to easily solved reasons. Nevertheless, when not detected ontime, the mineral sedimentation is almost unavoidable which results on the losses of resources.The electronic proposal to substitute the electromagnetic scraps is very cheap and easily to reproduce on the factory itself forthe needed elements are classic with no resistance and manufacture demands.

Cyanide poisoning of a Cooper’s hawk (Accipiter cooperii)

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Franson, J. Christian

2017-01-01

A Cooper’s hawk (Accipiter cooperii) was found dead in a ditch leading from a heap leach pad at a gold mine in Nevada. Observations at autopsy included an absence of external lesions, traces of subcutaneous and coronary fat, no food in the upper gastrointestinal tract, and no lesions in the viscera. Cyanide concentrations (µg/g ww) were 5.04 in blood, 3.88 in liver, and 1.79 in brain. No bacteria or viruses were isolated from tissues, and brain cholinesterase activity was within the normal range for a Cooper’s hawk.

Evita Perón y el Che Guevara: De la historia a la construcción literaria del mito biográfico

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Cecilia López Badano

2014-06-01

Full Text Available Eva Perón y el Che Guevara son dos de las figuras paradigmáticas argentinas, conocidas internacionalmente a través no sólo de sus vidas, que pueden reconstruirse a partir de documentos históricos, sino por el mito nacional - e internacional - que la muerte temprana ha configurado con ambos mediante la ayuda de la literatura y el cine, expandiendo ficcionalmente el matiz revolucionario de su accionar. El presente texto se propone, en consecuencia, dar cuenta de esas "capas" ficcionales que conforman la construcción estética de los dos mitos biográficos e inciden en la evaluación de sus protagonistas reales, modelando la percepción de ambos, particularmente, la considerada por el gran público más que por los especialistas.

Inhibition on cholinesterase and tyrosinase by alkaloids and phenolics from Aristotelia chilensis leaves.

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Cespedes, Carlos L; Balbontin, Cristian; Avila, Jose G; Dominguez, Mariana; Alarcon, Julio; Paz, Cristian; Burgos, Viviana; Ortiz, Leandro; Peñaloza-Castro, Ignacio; Seigler, David S; Kubo, Isao

2017-11-01

It is reported in this study the effect of isolates from leaves of Aristotelia chilensis as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase enzymes. The aim of the paper was to evaluate the activity of A. chilensis towards different enzymes. In addition to pure compounds, extracts rich in alkaloids and phenolics were tested. The most active F5 inhibited AChE (79.5% and 89.8% at 10.0 and 20.0 μg/mL) and against BChE (89.5% and 97.8% at 10.0 and 20.0 μg/mL), showing a strong mixed-type inhibition against AChE and BChE. F3 (a mixture of flavonoids and phenolics acids), showed IC 50 of 90.7 and 59.6 μg/mL of inhibitory activity against AChE and BChE, inhibiting the acetylcholinesterase competitively. Additionally, F3 showed and high potency as tyrosinase inhibitor with IC 50 at 8.4 μg/mL. Sample F4 (anthocyanidins and phenolic composition) presented a complex, mixed-type inhibition of tyrosinase with a IC 50 of 39.8 μg/mL. The findings in this investigation show that this natural resource has a strong potential for future research in the search of new phytotherapeutic treatments for cholinergic deterioration ailments avoiding the side effects of synthetic drugs. This is the first report as cholinesterases and tyrosinase inhibitors of alkaloids and phenolics from A. chilensis leaves. Copyright © 2017 Elsevier Ltd. All rights reserved.

Atomistic structural ensemble refinement reveals non-native structure stabilizes a sub-millisecond folding intermediate of CheY

International Nuclear Information System (INIS)

Shi, Jade; Schwantes, Christian; Bilsel, Osman

2017-01-01

The dynamics of globular proteins can be described in terms of transitions between a folded native state and less-populated intermediates, or excited states, which can play critical roles in both protein folding and function. Excited states are by definition transient species, and therefore are difficult to characterize using current experimental techniques. We report an atomistic model of the excited state ensemble of a stabilized mutant of an extensively studied flavodoxin fold protein CheY. We employed a hybrid simulation and experimental approach in which an aggregate 42 milliseconds of all-atom molecular dynamics were used as an informative prior for the structure of the excited state ensemble. The resulting prior was then refined against small-angle X-ray scattering (SAXS) data employing an established method (EROS). The most striking feature of the resulting excited state ensemble was an unstructured N-terminus stabilized by non-native contacts in a conformation that is topologically simpler than the native state. We then predict incisive single molecule FRET experiments, using these results, as a means of model validation. Our study demonstrates the paradigm of uniting simulation and experiment in a statistical model to study the structure of protein excited states and rationally design validating experiments.

Catalpol ameliorates beta amyloid-induced degeneration of cholinergic neurons by elevating brain-derived neurotrophic factors.

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Wang, Z; Liu, Q; Zhang, R; Liu, S; Xia, Z; Hu, Y

2009-11-10

The purpose of this work is to study the effect of catalpol, an iridoid from Rehmannia glutinosa on neurodegenerative changes induced by beta-amyloid peptide Abeta(25-35) or Abeta(25-35)+ibotenic acid and the underlying mechanism. Results showed that catalpol significantly improved the memory deficits in the neurodegenerative mouse model produced by injection of Abeta(25-35)+ibotenic acid to the nucleus magnocellularis basalis, yet it is neither a cholinesterase inhibitor nor a muscarinic (M) receptor agonist. Instead, the choline acetyl transferase (ChAT) activity and the M receptor density in brain were significantly decreased in the model mice and catalpol could significantly elevate their levels. Furthermore, the brain-derived neurotrophic factor (BDNF) content in brain was significantly decreased in the model mice and catalpol elevated it to normal level (83%+/-3% and 102%+/-2% of normal respectively). There is a significant positive correlation between BDNF content and memory. Primary culture of forebrain neurons revealed that aggregated Abeta(25-35) induced significant decrease of ChAT positive neuron number, neurite outgrowth length, and M receptor density, while catalpol added to the culture medium 2 h prior to Abeta addition showed significant dose dependent protective effect. Notably, 24 h and 48 h after the addition of Abeta to the cultured cells, the BDNF mRNA level in the neurons decreased to 76%+/-7% and 66%+/-3% of control without catalpol treatment, but became 128%+/-17% and 131%+/-23% of control with catalpol treatment. When the action of BDNF was inhibited by k252a in the cultured neurons, the protective effect of catalpol was completely (neurite outgrowth length) or partially (ChAT positive neuron number and the M receptor density) abolished. Taken together, catalpol improves memory and protects the forebrain neurons from neurodegeneration through increasing BDNF expression. Whether catalpol could reverse the neurodegenerative changes already

CLD (chronic liver diseases)-HbA1C as a suitable indicator for estimation of mean plasma glucose in patients with chronic liver diseases.

Science.gov (United States)

Koga, Masafumi; Kasayama, Soji; Kanehara, Hideo; Bando, Yukihiro

2008-08-01

In patients with chronic liver diseases (CLD), turnover of erythrocytes is increased whereas that of serum albumin is decreased. Thus, glycated hemoglobin (HbA(1C)) and glycated albumin (GA) cannot be used as adequate indicators for chronic plasma glucose control in diabetic patients with CLD. In this investigation, we have proposed CLD-HbA(1C), a novel long-term glycemic control marker by using measured HbA(1C) and GA. We studied 82 patients with CLD in whom glycemic control was regarded as to be stable. Daily plasma glucose profiles were monitored and estimated levels of HbA(1C) were calculated on the conversion formula established by Rohlfing et al. [C.L. Rohlfing, J.D. England, H.M. Wiedmeyer, A. Tennill, R.R. Little, D.E. Goldstein, Defining the relationship between plasma glucose and HbA1c, Diabetes Care 25 (2002) 275-278]. Cholinesterase (ChE) as an indicator for hepatic function was determined at the same time when HbA(1C) and GA levels were measured. CLD-HbA(1C) was defined as the average of measured HbA(1C) and GA/3, based upon the results that among healthy individuals, GA levels were roughly estimated at approximately threefold higher than HbA(1C) levels. While measured HbA(1C) levels in patients with CLD were generally lower than estimated HbA(1C) levels, GA/3 values were generally higher than estimated HbA(1C) levels. Such discrepancies lineally increased in accordance with a decrease in ChE levels. On the other hand, CLD-HbA(1C) levels were highly correlated with estimated HbA(1C) levels (R=0.883), while no significant correlation between CLD-HbA(1C) and ChE was noted. In conclusion, CLD-HbA(1C) has been found a superior chronic glycemic control marker than HbA(1C) or GA in diabetic patients with chronic liver diseases.

Synthesis, biological evaluation and docking studies of 2,3-dihydroquinazolin-4(1H)-one derivatives as inhibitors of cholinesterases.

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Sarfraz, Muhammad; Sultana, Nargis; Rashid, Umer; Akram, Muhammad Safwan; Sadiq, Abdul; Tariq, Muhammad Ilyas

2017-02-01

In search of potent inhibitors of cholinesterases, we have synthesized and evaluate a number of 2,3-dihydroquinazolin-4(1H)-one derivatives. The synthetic approach provided an efficient synthesis of the target molecules with excellent yield. All the tested compounds showed activity against both the enzymes in micromolar range. In many case, the inhibition of both enzymes are higher than or comparable to the standard drug galatamine. With the selectivity index of 2.3 for AChE, compound 5f can be considered as a potential lead compound with a feature of dual AChE/BChE inhibition with IC 50 =1.6±0.10μM (AChE) and 3.7±0.18μM (BChE). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. The computed binding modes of these compounds in the active site of AChE and BChE provide an insight into the mechanism of inhibition of these two enzyme. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of novel tacrine-related cholinesterase inhibitors in the reversal of 3-quinuclidinyl benzilate-induced cognitive deficit in rats--Is there a potential for Alzheimer's disease treatment?

Science.gov (United States)

Misik, Jan; Korabecny, Jan; Nepovimova, Eugenie; Kracmarova, Alzbeta; Kassa, Jiri

2016-01-26

Inhibitors of cholinesterase are important drugs for therapy of Alzheimer's disease and the search for new modifications is extensive, including dual inhibitors or multi-target hybrid compounds. The aim of the present study was a preliminary evaluation of pro-cognitive effects of newly-developed 7-MEOTA-donepezil like hybrids (compounds no. 1 and 2) and N-alkylated tacrine derivatives (compounds no. 3 and 4) using an animal model of pharmacologically-induced cognitive deficit. Male Wistar rats were subjected to tests of learning and memory in a water maze and step-through passive avoidance task. Cognitive impairment was induced by 3-quinuclidinyl benzilate (QNB, 2mgkg(-1)), administered intraperitoneally 1h before training sessions. Cholinesterase inhibitors were administered as a single therapeutic dose following the QNB at 30min at the following dose rates; 1 (25.6mgkg(-1)), 2 (12.3mgkg(-1)), 3 (5.7mgkg(-1)), 4 (5.2mgkg(-1)). The decrease in total path within the 10-swim session (water maze), the preference for target quadrant (water maze) and the entrance latency (passive avoidance) were taken as indicators of learning ability in rats. The effects of novel compounds were compared to that of standards tacrine (5.2mgkg(-1)) and donepezil (2.65mgkg(-1)). QNB significantly impaired spatial navigation as well as fear learning. Generally, the performance of rats was improved when treated with novel inhibitors and this effect reached efficiency of standard donepezil at selected doses. There was a significant improvement in the groups treated with compounds 2 and 3 in all behavioral tasks. The rest of the novel compounds succeed in the passive avoidance test. In summary, the potential of novel inhibitors (especially compounds 2 and 3) was proved and further detailed evaluation of these compounds as potential drugs for Alzheimer's disease treatment is proposed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Repeated Exposure to Neurotoxic Levels of Chlorpyriphos Alters Hippocampal Expression of Neurotrophins and Neuropeptides

Science.gov (United States)

2016-01-13

hormone bindi Bdnf BDNF Brain-derived neurotrophic factor Mdk MDK Midkine (neurite growth -promoting fa Rbp4 RBP4 Retinol binding protein 4, plasma...cause cholinergic crisis are associated with problems in cognitive function (i.e., learning and memory deficits ), but the biological mechanism(s...neurobehavioral deficits following subchronic exposure to CPF at a level that inhibits hippocampal cholinesterase to less than 20% of control. An equally

Nascita e destino della soggettività. Dai ruoli professionali ai processi di cura, attraverso una lettura di "Quel che resta del giorno" di Kazuo Ishiguro

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Gabriele Profita

2017-07-01

Full Text Available Questa riflessione affronta un tema assai rilevante per le professioni di cura, con uno sguardo particolare alla psicoterapia. Per chiarire il ruolo della soggettività e della nascita e maturazione di un ruolo professionale riporterò un’analisi di un testo letterario attraverso il quale sarà più agevole scoprire come si forma l’identità di un ruolo professionale e come si avvia alla sua maturazione e alla sua codificazione. In particolare quali sono i rischi legati ad una sua rigida codificazione rivolta alla sua normatività tecnica? Mi propongo di tracciare un confronto con alcune forme di costruzione della soggettività che nel corso dei secoli hanno fondato il modello dell’uomo occidentale nelle sue articolazioni professionali.

Synthesis, biological assessment and molecular modeling of new dihydroquinoline-3-carboxamides and dihydroquinoline-3-carbohydrazide derivatives as cholinesterase inhibitors, and Ca channel antagonists.

Science.gov (United States)

Tomassoli, Isabelle; Ismaili, Lhassane; Pudlo, Marc; de Los Ríos, Cristóbal; Soriano, Elena; Colmena, Inés; Gandía, Luis; Rivas, Luis; Samadi, Abdelouahid; Marco-Contelles, José; Refouvelet, Bernard

2011-01-01

The synthesis, biological evaluation, and molecular modeling of new 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides(4), 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbohydrazide (6), and some hexahydropyrimido[5,4-c]quinoline-2,5-diones (9) produced earlier by our laboratory, as AChE/BuChE inhibitors, is described. From these analyses compound 4c resulted equipotent regarding the inhibition of cholinesterases'; inhibitors 6k, 9a, 9b were selective for AChE, whereas product 4d proved selective for BuChE. Docking analysis has been carry out in order to identify the binding mode in the active site, and to explain the observed selectivities. Only compound 9a has been shown to decrease K(+)-induced calcium signals in bovine chromaffin cells. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Design, synthesis and biological evaluation of multifunctional tacrine-curcumin hybrids as new cholinesterase inhibitors with metal ions-chelating and neuroprotective property.

Science.gov (United States)

Liu, Zhikun; Fang, Lei; Zhang, Huan; Gou, Shaohua; Chen, Li

2017-04-15

Total sixteen tacrine-curcumin hybrid compounds were designed and synthesized for the purpose of searching for multifunctional anti-Alzheimer agents. In vitro studies showed that these hybrid compounds showed good cholinesterase inhibitory activity. Particularly, the potency of K 3-2 is even beyond tacrine. Some of the compounds exhibited different selectivity on acetylcholinesterase or butyrylcholinesterase due to the structural difference. Thus, the structure and activity relationship is summarized and further discussed based on molecular modeling studies. The ORAC and MTT assays indicated that the hybrid compounds possessed pronounced antioxidant activity and could effectively protect PC12 cells from the H 2 O 2 /Aβ42-induced toxicity. Moreover, the hybrid compounds also showed positive metal ions-chelating ability in vitro, suggesting a potential to halt ion-induced Aβ aggregation. All the obtained results demonstrated that the tacrine-curcumin hybrid compounds, in particular compound K 3-2 , can be considered as potential therapeutic agents for Alzheimer's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

La normativa italiana sui contratti di lavoro a tempo determinato nel settore della scuola è contraria al diritto dell’Unione: la Corte di Giustizia UE apre al risarcimento per i docenti che abbiano svolto supplenze annuali per la copertura di posti vacanti

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Arando Plaia

2015-01-01

Full Text Available La Corte di Giustizia UE con sentenza 26 novembre 2014, cause riunite C-22/13, C-61/13, C-62/13, C-63/13, C-418/13, Mascolo, ha ritenuto che la normativa europea sul lavoro a tempo determinato, applicabile anche al settore pubblico della scuola (casi Rosado Santana, Marrosu Sardino e Adelener, osta ad un sistema di assunzione per svolgere “supplenze annuali” nelle scuole pubbliche che non prevede almeno una delle seguenti “misure di prevenzione”: l’indicazione delle “ragioni oggettive” che giustificano il rinnovo dei contratti; la determinazione della “durata massima totale dei contratti” o del “numero dei loro rinnovi”, in assenza peraltro di una misura sanzionatoria proporzionata, effettiva e dissuasiva, da applicarsi in caso di utilizzo abusivo di successione di contratti a tempo determinato (clausola 5 dell’accordo quadro 18 marzo 1999 allegato dir. 1999/70/CE. Sebbene dunque il settore dell’insegnamento implichi inevitabilmente una certa “flessibilità”, e la normativa europea non enunci un obbligo generale degli Stati membri di prevedere la sanzione della trasformazione dei contratti di lavoro a tempo determinato in contratti a tempo indeterminato (CGUE 3 luglio 2014, Fiamingo, causa C-362/13, la normativa italiana non prevede misure atte a “prevenire” o “sanzionare” l’utilizzo abusivo di successione di contratti a tempo determinato. Questo (e non altro il principio di diritto affermato dalla Corte di giustizia: la sentenza ribadisce l’assenza di misure di prevenzione imposte dalla disciplina europea nonché di una sanzione risarcitoria rispetto al ricorso abusivo ai contratti a tempo determinato nel settore scolastico.

Effects of xenobiotic compounds on the cell activities of Euplotes crassus, a single-cell eukaryotic test organism for the study of the pollution of marine sediments

International Nuclear Information System (INIS)

Trielli, Francesca; Amaroli, Andrea; Sifredi, Francesca; Marchi, Barbara; Falugi, Carla; Corrado, Maria Umberta Delmonte

2007-01-01

It is now widely accepted that assays with protists are relevant to be exploited for the study of environmental modifications due to the presence of xenobiotic compounds. In this work, the possibility of utilizing Euplotes crassus, an interstitial marine ciliate, for the pre-chemical screening of estuarine and coastal sediments was evaluated. For this purpose, the effects of exposure to pollutants were tested on the cell viability, fission rate and lysosomal membrane stability of E. crassus. The following toxicants were used: an organophosphate (OP) pesticide, basudin, an organochlorine hydrocarbon, AFD25, both employed especially for pest control in agricultural sites, a toxic heavy metal, mercury (HgCl 2 ) and different mixtures of the above-mentioned compounds, as they might occur in polluted sites. Exposure to these toxicants affected cell viability at concentrations ranging from 96.6 to 966 x 10 3 mg/l for basudin, from 3.3 to 33 x 10 3 mg/l for AFD25 and from 0.1 to 1 mg/l for HgCl 2 . A significant decrease in the mean fission rate (P -2 mg/l HgCl 2 . Furthermore, the Neutral Red Retention Assay showed a significant decrease in lysosomal membrane stability after 60- and 120-min exposures to AFD25 (33 mg/l) and HgCl 2 (0.33 mg/l). In addition, as it is well-known that the inhibition of acetylcholinesterase activity represents a specific biomarker of exposure to OP and carbamate pesticides in higher organisms, initially the presence of cholinesterase (ChE) activity was detected in E. crassus, using cytochemical, spectrophotometric and electrophoretic methods. Afterwards, this enzyme activity was characterized spectrophotometrically by its sensitivity to specific ChE inhibitors and to variations in pH and temperature. The ChE activity was inhibited significantly by basudin- (9.66 and 96.6 mg/l) or AFD25-exposure (3.3 mg/l). Conversely, exposure to AFD25 (33 mg/l) or HgCl 2 (0.1 and 0.3 mg/l) caused a significant increase in this enzyme activity. Moreover

Chemical and radiological effects of chronic ingestion of uranium in the rat brain: biochemical impairment of dopaminergic, serotonergic and cholinergic neuro-transmissions; Effets chimique et radiologique d'une ingestion chronique d'uranium sur le cerveau du rat. Effets sur les neurotransmissions dopaminergique, serotoninergique et cholinergique

Energy Technology Data Exchange (ETDEWEB)

Bussy, C

2005-09-15

Uranium is an environmental ubiquitous metal-trace element. It has both chemical and radiological toxicity. After chronic ingestion, uranium can distribute in any part of the body and accumulate in the brain. The aims of this study was 1) to determine and estimate the effects of uranium on dopaminergic, serotoninergic and cholinergic systems and 2) to measure the uranium amount in the brain, after chronic exposure by ingestion of depleted (D.U.) or enriched (E.U.) uranium during 1.5 to 18 months at 40 mg.L{sup -1} (40 ppm) in different rat brain areas. At any time of exposure, the results show that both the neurotransmission alterations and the uranium brain accumulation were moderate, area specific, time-evolutive and depended on uranium specific activity. After D.U. exposure, monoamine perturbations are chronic and progressive. On the contrary, monoamine alterations occurred only after long term of E.U. exposure. These mono-aminergic modifications are not always dependent on uranium accumulation in brain areas. Moreover, although the cholinergic system was not affected at both 1.5 and 9 months of D.U. exposure, the alteration of ChE activity after E.U. exposure are both dependent on uranium accumulation in brain areas and on uranium specific activity. After E.U. exposure, cholinergic modification and uranium accumulation in hippocampus could partially explain the short-term memory disturbances which have been previously reported. (author)

Effects of Two-Year Treatment with the Cholinesterase Inhibitor Rivastigmine on Behavioural Symptoms in Alzheimer’s Disease

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Michael Rösler

1999-01-01

Full Text Available Alzheimer’s disease (AD is accompanied by prominent behavioural disturbances. They cause significant distress for both caregivers and patients and can play a major role in the decision to institutionalise AD patients. Recent evidence suggests that cholinergic deficiencies not only contribute to the memory and cognitive abnormalities of AD but are also responsible for some behavioural abnormalities seen over the course of the disease. In this study we assessed the ability of rivastigmine, a pseudo-irreversible cholinesterase inhibitor, to improve behavioural and psychopathologic symptoms in AD. The analysis included 34 patients present in the Germanarm of the international study B303 who received and completed long-term treatment with rivastigmine in the open-label study B305. Assessments of behaviour and psychopathological symptoms were performed using the behavioural component of the Clinicians Interview Based Impression of Change Plus (CIBIC-Plus. Results show that long-term treatment with rivastigmine can slow the progression of behavioural and psychopathological symptoms of AD. Behavioural symptoms showing stabilisation included aggressiveness, activity disturbances, hallucinations and paranoid features. Results also suggest that patients treated earlier with rivastigmine may attain a greater benefit compared with patients whose treatment is delayed 6 months. Further studies examining the effects of rivastigmine on behavioural disturbances in AD are therefore warranted.

Chemical and radiological effects of chronic ingestion of uranium in the rat brain: biochemical impairment of dopaminergic, serotonergic and cholinergic neuro-transmissions; Effets chimique et radiologique d'une ingestion chronique d'uranium sur le cerveau du rat. Effets sur les neurotransmissions dopaminergique, serotoninergique et cholinergique

Energy Technology Data Exchange (ETDEWEB)

Bussy, C

2005-09-15

Uranium is an environmental ubiquitous metal-trace element. It has both chemical and radiological toxicity. After chronic ingestion, uranium can distribute in any part of the body and accumulate in the brain. The aims of this study was 1) to determine and estimate the effects of uranium on dopaminergic, serotoninergic and cholinergic systems and 2) to measure the uranium amount in the brain, after chronic exposure by ingestion of depleted (D.U.) or enriched (E.U.) uranium during 1.5 to 18 months at 40 mg.L{sup -1} (40 ppm) in different rat brain areas. At any time of exposure, the results show that both the neurotransmission alterations and the uranium brain accumulation were moderate, area specific, time-evolutive and depended on uranium specific activity. After D.U. exposure, monoamine perturbations are chronic and progressive. On the contrary, monoamine alterations occurred only after long term of E.U. exposure. These mono-aminergic modifications are not always dependent on uranium accumulation in brain areas. Moreover, although the cholinergic system was not affected at both 1.5 and 9 months of D.U. exposure, the alteration of ChE activity after E.U. exposure are both dependent on uranium accumulation in brain areas and on uranium specific activity. After E.U. exposure, cholinergic modification and uranium accumulation in hippocampus could partially explain the short-term memory disturbances which have been previously reported. (author)

The CheMin XRD on the Mars Science Laboratory Rover Curiosity: Construction, Operation, and Quantitative Mineralogical Results from the Surface of Mars

Science.gov (United States)

Blake, David F.

2015-01-01

The Mars Science Laboratory mission was launched from Cape Canaveral, Florida on Nov. 26, 2011 and landed in Gale crater, Mars on Aug. 6, 2012. MSL's mission is to identify and characterize ancient "habitable" environments on Mars. MSL's precision landing system placed the Curiosity rover within 2 km of the center of its 20 X 6 km landing ellipse, next to Gale's central mound, a 5,000 meter high pile of laminated sediment which may contain 1 billion years of Mars history. Curiosity carries with it a full suite of analytical instruments, including the CheMin X-ray diffractometer, the first XRD flown in space. CheMin is essentially a transmission X-ray pinhole camera. A fine-focus Co source and collimator transmits a 50µm beam through a powdered sample held between X-ray transparent plastic windows. The sample holder is shaken by a piezoelectric actuator such that the powder flows like a liquid, each grain passing in random orientation through the beam over time. Forward-diffracted and fluoresced X-ray photons from the sample are detected by an X-ray sensitive Charge Coupled Device (CCD) operated in single photon counting mode. When operated in this way, both the x,y position and the energy of each photon are detected. The resulting energy-selected Co Kalpha Debye-Scherrer pattern is used to determine the identities and amounts of minerals present via Rietveld refinement, and a histogram of all X-ray events constitutes an X-ray fluorescence analysis of the sample.The key role that definitive mineralogy plays in understanding the Martian surface is a consequence of the fact that minerals are thermodynamic phases, having known and specific ranges of temperature, pressure and composition within which they are stable. More than simple compositional analysis, definitive mineralogical analysis can provide information about pressure/temperature conditions of formation, past climate, water activity and the like. Definitive mineralogical analyses are necessary to establish

Cholinesterase inhibitor use is associated with increased plasma levels of anti-Aβ 1-42 antibodies in Alzheimer's disease patients.

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Conti, Elisa; Galimberti, Gloria; Tremolizzo, Lucio; Masetto, Alessandro; Cereda, Diletta; Zanchi, Clara; Piazza, Fabrizio; Casati, Marco; Isella, Valeria; Appollonio, Ildebrando; Ferrarese, Carlo

2010-12-17

Acetyl-cholinesterase inhibitors (AChEI) are drugs frequently prescribed for the treatment of Alzheimer's disease (AD), exerting an effect on cognition, as well as on behavioural and psychological symptoms of dementia and activities of daily living. The efficacy of AChEI may be ascribed not only to the activation of cholinergic transmission, but also to other mechanisms, among which a putative regulation of the immune response has already been hypothesized. In the present study, we evaluated, in a cross-sectional sample of 66AD patients and 48 healthy controls, the putative influence of AChEI on anti-Abeta 1-42 antibody plasma levels by ELISA assay. AD patients receiving AChEI therapy showed increased plasma levels of anti-Abeta 1-42 antibodies respect to untreated AD patients and antibodies levels similar to those of healthy controls, both before and after normalization by total IgG values. Our results support a potential role of AChEI in the modulation of the immune response against Abeta. We suggest that a strategy aimed at increasing the endogenous response against this peptide might represent an interesting therapeutic target to be further investigated. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Potentiation by cholinesterase inhibitors of cholinergic activity in rat isolated stomach and colon.

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Jarvie, Emma M; Cellek, Selim; Sanger, Gareth J

2008-01-01

Acetylcholinesterase (AChE) inhibitors stimulate gastrointestinal (GI) motility and are potential treatments of conditions associated with inadequate GI motility. The ability of itopride to facilitate neuronally (predominantly cholinergic) mediated contractions of rat isolated stomach, evoked by electrical field stimulation (EFS), has been compared with other cholinesterase inhibitors and with tegaserod, a clinically effective prokinetic and non-selective 5-HT(4) receptor agonist which also facilitates GI cholinergic function. Neostigmine greatly increased EFS-evoked contractions over a narrow concentration range (0.01-1 microM; 754+/-337% facilitation at 1 microM); higher concentrations (1, 3 microM) also increased muscle tension. Donepezil increased EFS-evoked contractions gradually over the full range of concentrations (0.01-10 microM; maximum increase 516+/-20% at 10 microM). Itopride increased the contractions even more gradually, rising to 188+/-84% at 10 microM. The butyrylcholinesterase inhibitor iso-OMPA 0.01-10 microM also increased EFS-evoked contractions, to a maximum of 36+/-5.0% at 10 microM, similar to that caused by tegaserod (35+/-5.2% increase at 1 microM). The effects of tegaserod, but not itopride were inhibited by the 5-HT(4) receptor antagonist SB-204070A 0.3 microM. In rat isolated colon, neostigmine was again the most efficacious, causing a defined maximum increase in EFS-evoked contractions (343+/-82% at 10 microM), without changing muscle tension. Maximum increases caused by donepezil and itopride were, respectively, 57.6+/-20 and 43+/-15% at 10 microM. These data indicate that the abilities of different AChE inhibitors to increase GI cholinergic activity differ markedly. Understanding the reasons is essential if AChE inhibitors are to be optimally developed as GI prokinetics.

Functional response to cholinesterase inhibitor therapy in a naturalistic Alzheimer’s disease cohort

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Wattmo Carina

2012-11-01

Full Text Available Abstract Background Activities of daily living (ADL are an essential part of the diagnostic criteria for Alzheimer’s disease (AD. A decline in ADL affects independent living and has a strong negative impact on caregiver burden. Functional response to cholinesterase inhibitor (ChEI treatment and factors that might influence this response in naturalistic AD patients need investigating. The aim of this study was to identify the socio-demographic and clinical factors that affect the functional response after 6 months of ChEI therapy. Methods This prospective, non-randomised, multicentre study in a routine clinical setting included 784 AD patients treated with donepezil, rivastigmine or galantamine. At baseline and after 6 months of treatment, patients were assessed using several rating scales, including the Instrumental Activities of Daily Living (IADL scale, Physical Self-Maintenance Scale (PSMS and Mini-Mental State Examination (MMSE. Demographic and clinical characteristics were investigated at baseline. The functional response and the relationships of potential predictors were analysed using general linear models. Results After 6 months of ChEI treatment, 49% and 74% of patients showed improvement/no change in IADL and in PSMS score, respectively. The improved/unchanged patients exhibited better cognitive status at baseline; regarding improved/unchanged PSMS, patients were younger and used fewer anti-depressants. A more positive functional response to ChEI was observed in younger individuals or among those having the interaction effect of better preserved cognition and lower ADL ability. Patients with fewer concomitant medications or those using NSAIDs/acetylsalicylic acid showed a better PSMS response. Conclusions Critical characteristics that may influence the functional response to ChEI in AD were identified. Some predictors differed from those previously shown to affect cognitive response, e.g., lower cognitive ability and older age

A look at the hepatic encephalopathy in cirrhosis

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Giacomo Zaccherini

2013-01-01

Full Text Available Hepatic encephalopathy (HE is a neuropsychiatric syndrome complicating acute and chronic liver failure and characterized by a wide range of manifestations, in absence of other brain disease. HE is very frequent in course of cirrhosis and even mild forms involve a great additional burden on patients, their families and health-care resources. Its onset affects subsequent survival of patients. Historically, pathophysiology of HE was connected to several substances (mostly ammonia produced in the gut and normally metabolized by the liver, but more recently other factors such as inflammation, bacterial translocation and oxidative stress have shown a crucial role. Symptoms are often overt (confusion, asterixis, disorientation, ataxia or coma but can also be subtle (sleep disturbances, cognitive impairment, mood alterations, impairment of executive decision-making, and psychomotor speed – Minimal HE; the West Haven Criteria are most often used to grade Overt HE (OHE, with grade ranging from 0 to 4 (4 corresponding to coma. Since both Minimal HE and grade 1 HE cannot be diagnosed by clinical examination and need for specific tests, it results practical to combine these entities and name them "Covert" HE (CHE to aid clinical use. Diagnosis is based on evidence of neurological impairment in presence of liver cirrhosis, only after the exclusion of other brain diseases. Measurement of serum ammonia and electroencephalography are little specific, while brain magnetic resonance and search for portosystemic shunts are important in complex cases. Diagnosis of OHE is often just clinical, while that of CHE requires dedicated psychometric and neurophysiological tests. Although these tests are difficult to be performed in the clinical practice, detection and treatment of CHE are cost-effective and important; indeed, CHE affects patients’ quality of life, socioeconomic status and driving skills, and increases the risk for falls, car accidents, development of OHE

Susceptibility of various areas of the nervous system of hens to TOCP-induced delayed neuropathy.

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Classen, W; Gretener, P; Rauch, M; Weber, E; Krinke, G J

1996-01-01

Sensitivity of in-life parameters, biochemical endpoints, and susceptibility of various areas of the chicken nervous system to delayed neuropathy induced by tri-orthocresyl phosphate (TOCP) was assessed. Groups of hens were exposed to a single oral dose of TOCP of 0, 50, 200 or 500 mg/kg and the animals observed for 21 days. Perfusion fixed, paraffin embedded tissue sections were stained with Bodian's silver and Luxol blue and semi-thin epoxy sections with toluidine blue. Sciatic and tibial nerves, lumbosacral, midthoracic, and upper cervical spinal cord, medulla oblongata and cerebellum were examined using a semiquantitative scoring system. In pair-dosed hens inhibition of brain and spinal cord neurotoxic esterase (NTE) and cholinesterase and of plasma and erythrocyte cholinesterases was determined 24 hr and 48 hr after administration. At all dose levels NTE in brain and spinal cord and plasma cholinesterase was inhibited markedly. Quantitative inhibition of NTE was seen also in absence of neuropathy. Ataxia and body weight loss occurred in high-dose animals only, while dose-related neuropathy was seen in the distal tibial nerve, medulla oblongata and cerebellum. Ataxia was correlated best with neuropathy in peripheral nerves while degeneration of nerve fibers in the cerebellum, seen best in mid-longitudinal sections, was the most sensitive histological indicator of TOCP-induced delayed neuropathy. The particular susceptibility of spinocerebellar neurons was recognized long ago, but often has been neglected in delayed neurotoxicity studies and respective guidelines. Optimal sensitivity of toxicity tests is a prerequisite for risk assessment, can be cost efficient, and nowadays should be a main interest of animal welfare in order to reduce animals' suffering. Based on these data, determination of NTE inhibition together with histopathological examination of longitudinal sections of distal tibial nerves, mid-longitudinal sections of rostral cerebellum and cross

Cholinergic modulation of visual and attentional brain responses in Alzheimer's disease and in health

OpenAIRE

Bentley, P.; Driver, J.; Dolan, R.J.

2007-01-01

Visuo-attentional deficits occur early in Alzheimer's disease (AD) and are considered more responsive to pro-cholinergic therapy than characteristic memory disturbances. We hypothesised that neural responses in AD during visual attentional processing would be impaired relative to controls, yet partially susceptible to improvement with cholinesterase inhibition. We studied 16 mild AD patients and 17 age-matched healthy controls, using fMRI-scanning to enable within-subject placebo-controlled c...

Rock shelter occupation during isotopic stage 5: level D of the site of Payre (Ardèche, France. Territorial organisation and intra-site activities

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Moncel, Marie-Hélène

2007-06-01

Full Text Available This paper presents the results obtained from an interdisciplinary study of the level D archaeological assemblages from Payre (Ardèche, France. This site is dated to the final of OIS 6 and the beginning of OIS 5. The combined analysis of the lithic and faunal assemblages accumulated and their management “into” and “out of” the site gives a better understanding of the behaviour of the Neanderthal groups that inhabited it. This study has allowed us to correlate the territorial exploitation for game hunting and for raw material procurement, within the context of seasonal short term occupations probably during the end of autumn and the beginning of winter.  

Este artículo presenta los resultados obtenidos a través del estudio multidisciplinar del registro arqueológico del nivel D del yacimiento de Payre (Ardèche, Francia datado entre el final del OIS 6 y el comienzo del OIS 5. El análisis conjunto de la industria lítica y de los restos óseos recuperados en el yacimiento y de la gestión de dichos recursos dentro y fuera de él, ha hecho posible la comprensión de los comportamientos humanos de los grupos neandertales que lo ocuparon. Dicho estudio nos ha permitido poner en relación el tipo de explotación del territorio de caza y de captación de materias primas, dentro del marco de ocupaciones estacionales de corta duración desarrolladas probablemente entre el final del otoño y el principio del invierno.  

LA DIAGNOSI DELLE COMPETENZE LINGUISTICHE IN UN CONTESTO MULTILINGUE: UN PROCESSO CONTINUO CHE FAVORISCE L’INSEGNAMENTO E L’APPRENDIMENTO INDIVIDUALIZZATO

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Drorit Lengyel

2011-07-01

Full Text Available Il presente studio affronta il problema della valutazione diagnostica delle competenze linguistiche in contesti educativi multilingui, con particolare attenzione ai bisogni dei bambini e degli adolescenti immigrati. Vengono brevemente esposti gli obiettivi, le funzioni e i principi della valutazione diagnostica e della valutazione formativa considerate parte integrante di una educazione linguistica continua che prevede un insegnamento-apprendimento individualizzato. Sul piano teorico le procedure della valutazione diagnostica delle competenze linguistiche in contesti multilingui fanno riferimento all’apprendimento delle lingue inteso come attività socio-culturale.     Language diagnostics in multilingual settings with respect to continuous procedures as accompaniment of individualized learning and teaching   This study provides an introduction to language diagnostics in multilingual educational settings, with particular reference to the needs of children and adolescents from migrant backgrounds. It summarises the objectives and functions of language diagnostics and the principles that govern diagnostics including formative assessment, considered to be an integral part of continuous language education that emphasises individualised teaching and learning. From a theoretical perspective, diagnostic procedures in multilingual settings treat language learning as a socio-cultural activity.  

Memory-enhancing activity of Anacyclus pyrethrum in albino Wistar rats

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K Sujith

2012-08-01

Full Text Available Objective: To explore the potential effect of ethanolic extract of Anacyclus pyrethrum (A. pyrethrum in memory dysfunction. Methods: Memory impairment was produced by administration of scopolamine (1mg/kg i. p in rats. Passive avoidance paradigms, elevated plus maze and social learning task was used to assess learning and memory. Results: A. pyrethrum extract treated group decreased transfer latency in elevated plus maze model paradigm which is an indicative of cognition improvement. In case of passive avoidance paradigm extract treated group exhibited prounced effect in reversal of scopolamine induced amnesia which was revealed by increase in step down latency. Social learning task also revealed the memory enhancing activity of A. pyrethrum extract. Conclusions: Ethanolic extract of A. pyrethrum has been demonstrated to improve cognitive processes by enhancing memory in different experimental paradigms such as passive avoidance paradigms, elevated plus maze and social learning task when administered orallyBrain cholinesterase level was measured to assess central cholinergic activity. The treatment with drugs, which increase cholinergic neurotransmission, causes an improvement in cognitive deficits. The present study suggest that ethanolic extract of A. pyrethrum increased brain cholinesterase level and hence it possess memory enhancing activity in scopolamine induced amnesia model by enhancing central cholinergic neurotransmission.

Brain/MINDS: brain-mapping project in Japan

Science.gov (United States)

Okano, Hideyuki; Miyawaki, Atsushi; Kasai, Kiyoto

2015-01-01

There is an emerging interest in brain-mapping projects in countries across the world, including the USA, Europe, Australia and China. In 2014, Japan started a brain-mapping project called Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS). Brain/MINDS aims to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain, and takes advantage of a unique non-human primate animal model, the common marmoset (Callithrix jacchus). In Brain/MINDS, the RIKEN Brain Science Institute acts as a central institute. The objectives of Brain/MINDS can be categorized into the following three major subject areas: (i) structure and functional mapping of a non-human primate brain (the marmoset brain); (ii) development of innovative neurotechnologies for brain mapping; and (iii) human brain mapping; and clinical research. Brain/MINDS researchers are highly motivated to identify the neuronal circuits responsible for the phenotype of neurological and psychiatric disorders, and to understand the development of these devastating disorders through the integration of these three subject areas. PMID:25823872

Brain/MINDS: brain-mapping project in Japan.

Science.gov (United States)

Okano, Hideyuki; Miyawaki, Atsushi; Kasai, Kiyoto

2015-05-19

There is an emerging interest in brain-mapping projects in countries across the world, including the USA, Europe, Australia and China. In 2014, Japan started a brain-mapping project called Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS). Brain/MINDS aims to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain, and takes advantage of a unique non-human primate animal model, the common marmoset (Callithrix jacchus). In Brain/MINDS, the RIKEN Brain Science Institute acts as a central institute. The objectives of Brain/MINDS can be categorized into the following three major subject areas: (i) structure and functional mapping of a non-human primate brain (the marmoset brain); (ii) development of innovative neurotechnologies for brain mapping; and (iii) human brain mapping; and clinical research. Brain/MINDS researchers are highly motivated to identify the neuronal circuits responsible for the phenotype of neurological and psychiatric disorders, and to understand the development of these devastating disorders through the integration of these three subject areas.

Fibroblast growth factor 21 protects mouse brain against D-galactose induced aging via suppression of oxidative stress response and advanced glycation end products formation.

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Yu, Yinhang; Bai, Fuliang; Wang, Wenfei; Liu, Yaonan; Yuan, Qingyan; Qu, Susu; Zhang, Tong; Tian, Guiyou; Li, Siming; Li, Deshan; Ren, Guiping

2015-06-01

Fibroblast growth factor 21 (FGF21) is a hormone secreted predominantly in the liver, pancreas and adipose tissue. Recently, it has been reported that FGF21-Transgenic mice can extend their lifespan compared with wild type counterparts. Thus, we hypothesize that FGF21 may play some roles in aging of organisms. In this study d-galactose (d-gal)-induced aging mice were used to study the mechanism that FGF21 protects mice from aging. The three-month-old Kunming mice were subcutaneously injected with d-gal (180mg·kg(-1)·d(-1)) for 8weeks and administered simultaneously with FGF21 (1, 2 or 5mg·kg(-1)·d(-1)). Our results showed that administration of FGF21 significantly improved behavioral performance of d-gal-treated mice in water maze task and step-down test, reduced brain cell damage in the hippocampus, and attenuated the d-gal-induced production of MDA, ROS and advanced glycation end products (AGEs). At the same time, FGF21 also markedly renewed the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total anti-oxidation capability (T-AOC), and decreased the enhanced total cholinesterase (TChE) activity in the brain of d-gal-treated mice. The expression of aldose reductase (AR), sorbitol dehydrogenase (SDH) and member-anchored receptor for AGEs (RAGE) declined significantly after FGF21 treatment. Furthermore, FGF21 suppressed inflamm-aging by inhibiting IκBα degradation and NF-κB p65 nuclear translocation. The expression levels of pro-inflammatory cytokines, such as TNF-α and IL-6, decreased significantly. In conclusion, these results suggest that FGF21 protects the aging mice brain from d-gal-induced injury by attenuating oxidative stress damage and decreasing AGE formation. Copyright © 2015 Elsevier Inc. All rights reserved.

Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?

International Nuclear Information System (INIS)

Liu Jing; Gupta, Ramesh C.; Goad, John T.; Karanth, Subramanya; Pope, Carey

2007-01-01

Glucose feeding can markedly exacerbate the toxicity of the anticholinesterase insecticide, parathion. We determined the effects of parathion on brain nitric oxide and its possible role in potentiation of toxicity by glucose feeding. Adult rats were given water or 15% glucose in water for 3 days and challenged with vehicle or parathion (18 mg/kg, s.c.) on day 4. Functional signs, plasma glucose and brain cholinesterase, citrulline (an indicator of nitric oxide production) and high-energy phosphates (HEPs) were measured 1-3 days after parathion. Glucose feeding exacerbated cholinergic toxicity. Parathion increased plasma glucose (15-33%) and decreased cortical cholinesterase activity (81-90%), with no significant differences between water and glucose treatment groups. In contrast, parathion increased brain regional citrulline (40-47%) and decreased HEPs (18-40%) in rats drinking water, with significantly greater changes in glucose-fed rats (248-363% increase and 31-61% decrease, respectively). We then studied the effects of inhibiting neuronal nitric oxide synthase (nNOS) by 7-nitroindazole (7NI, 30 mg/kg, i.p. x4) on parathion toxicity and its modulation by glucose feeding. Co-exposure to parathion and 7NI led to a marked increase in cholinergic signs of toxicity and lethality, regardless of glucose intake. Thus, glucose feeding enhanced the accumulation of brain nitric oxide following parathion exposure, but inhibition of nitric oxide synthesis was ineffective at counteracting increased parathion toxicity associated with glucose feeding. Evidence is therefore presented to suggest that nitric oxide may play both toxic and protective roles in cholinergic toxicity, and its precise contribution to modulation by glucose feeding requires further investigation

Thyrotoxic Dysphagia in an 82-Year-Old Male

OpenAIRE

Parperis, Konstantinos; Dadu, Ramona; Hoq, Sheikh; Argento, Vivian

2011-01-01

Dysphagia is a common problem in elderly patients and a rare manifestation of Graves' disease. We report a case of an 82-year-old male who presented with a 4-week history of dysphagia and weight loss. Workup for his dysphagia with upper endoscopy, MRI brain, electromyography, acetyl-cholinesterase receptor antibodies, and voltage-gated calcium channel antibodies were negative. Modified Barium swallow test showed oropharyngeal dysphagia. Thyroid function tests that revealed hyperthyroidism and...

Seasonal distribution of bird populations at the Patuxent Research Refuge

Science.gov (United States)

Hoffman, D.J.; Henny, C.J.; Hill, E.F.; Keith, J.A.; Grove, R.A.

2000-01-01

High concentrations of mercury from past mining activities have accumulated in the food chain of fish-eating birds nesting along the mid to lower Carson River. Activities of nine plasma and tissue enzymes, and concentrations of other plasma and tissue constituents were measured for black-crowned night-heron, Nycticorax nycticorax, (BCNH) and snowy egret, Egretta thula, (SE) nestlings from two high mercury sites and one low mercury site. Geometric mean blood Hg concentrations for BCNHs at the high mercury sites were 2.6 and 2.8 ppm (ww) and 0.6 ppm at the low mercury site. Blood concentrations for SEs were 3.6 and 1.9 ppm at the high mercury sites and 0.7 ppm at the low mercury site. In BCNHs plasma glutathione peroxidase (GSH peroxidase) activity was lower in both high mercury sites relative to the low mercury site. Butyryl cholinesterase (BuChe), ALT, glutathione reductase (GSSG-reductase) and LDH-L activities were lower in one high mercury site. In SEs significant differences were lower BuChe and LDH-L, but elevated GGT activities. Evidence of renal stress in both species at high mercury sites included increased plasma uric acid, blood urea nitrogen, and creatinine concentrations as well as oxidative stress in the kidney tissue itself where oxidized glutathione increased. A number of the mercury site-related effects, including decreased plasma GSH-peroxidase and hepatic G-6-PDH activities, higher GSSG-reductase activity, and lower hepatic concentrations of reduced thiols have been reported in methylmercury feeding studies with great egrets and mallards. These findings suggest the utility of herons and egrets for monitoring mercury sites.

Comparative chemical profiling, cholinesterase inhibitions and anti-radicals properties of essential oils from Polygonum hydropiper L: a preliminary anti- Alzheimer's study.

Science.gov (United States)

Ayaz, Muhammad; Junaid, Muhammad; Ullah, Farhat; Sadiq, Abdul; Khan, Mir Azam; Ahmad, Waqar; Shah, Muhammad Raza; Imran, Muhammad; Ahmad, Sajjad

2015-11-04

Cholinesterase inhibition is a vital target for the development of novel and mechanism based inhibitors, owing to their role in the breakdown of acetylcholine (ACh) neurotransmitter to treat various neurological disorders including Alzheimer's disease (AD). Similarly, free radicals are implicated in the progression of various diseases like neurodegenerative disorders. Due to lipid solubility and potential to easily cross blood brain barrier, this study was designed to investigate the anticholinesterase and antioxidant potentials of the standardized essential oils from the leaves and flowers of Polygonum hydropiper. Essential oils from the leaves (Ph.LO) and flowers (Ph.FO) of P. hdropiper were isolated using Clevenger apparatus. Oil samples were analyzed by GC-MS to identify major components and to attribute the antioxidant and anticholinesterase activity to specific components. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potentials of the samples were determined following Ellman's assay. Antioxidant assays were performed using 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS) and hydrogen peroxide (H2O2) free radical scavenging assays. In the GC-MS analysis 141 and 122 compounds were indentified in Ph.LO and Ph.FO respectively. Caryophylene oxide (41.42 %) was the major component in Ph.FO while decahydronaphthalene (38.29 %) was prominent in Ph.LO. In AChE inhibition, Ph.LO and Ph.FO exhibited 87.00** and 79.66***% inhibitions at 1000 μg/ml with IC50 of 120 and 220 μg/ml respectively. The IC50 value for galanthamine was 15 μg/ml. In BChE inhibitory assay, Ph.LO and Ph.FO caused 82.66*** (IC50 130 μg/ml) and 77.50***% (IC50 225 μg/ml) inhibitions respectively at 1000 μg/ml concentration. In DPPH free radical scavenging assay, Ph.LO and Ph.FO exhibited IC50 of 20 and 200 μg/ml respectively. The calculated IC50s were 180 & 60 μg/ml for Ph.LO, and 45 & 50 μg/ml for Ph.FO in scavenging

Synthesis and Biological Assessment of Racemic Benzochromenopyrimidinimines as Antioxidant, Cholinesterase, and Aβ1-42 Aggregation Inhibitors for Alzheimer's Disease Therapy.

Science.gov (United States)

Dgachi, Youssef; Ismaili, Lhassane; Knez, Damijan; Benchekroun, Mohamed; Martin, Hélène; Szałaj, Natalia; Wehle, Sarah; Bautista-Aguilera, Oscar M; Luzet, Vincent; Bonnet, Alexandre; Malawska, Barbara; Gobec, Stanislav; Chioua, Mourad; Decker, Michael; Chabchoub, Fakher; Marco-Contelles, José

2016-06-20

Given the complex nature of Alzheimer's disease (AD), compounds that are able to simultaneously address two or more AD-associated targets show greater promise for development into drugs for AD therapy. Herein we report an efficient two-step synthesis and biological evaluation of new racemic benzochromene derivatives as antioxidants, inhibitors of cholinesterase and β-amyloid (Aβ1-42 ) aggregation. Based on the results of the primary screening, we identified 15-(3-methoxyphenyl)-9,11,12,15-tetrahydro-10H,14H-benzo[5,6]chromeno[2,3-d]pyrido[1,2-a]pyrimidin-14-imine (3 e) and 16-(3-methoxyphenyl)-9,10,11,12,13,16-hexahydro-15H-benzo[5',6']chromeno[2',3':4,5]pyrimido[1,2-a]azepin-15-imine (3 f) as new potential multitarget-directed ligands for AD therapy. Further in-depth biological analysis showed that compound 3 f is a good human acetylcholinesterase inhibitor [IC50 =(0.36±0.02) μm], has strong antioxidant activity (3.61 μmol Trolox equivalents), and moderate Aβ1-42 antiaggregating power (40.3 %). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Colinesterasas eritrocitaria y plasmática en trabajadores con enfermedades crónicas controladas y en usuarios de medicamentos Erythrocytic and plasmatic cholinesterases in workers with chronic controlled diseases and in users of medicines

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Jaime Carmona Fonseca

2006-01-01

nunca hubo diferencia significativa. Tampoco hubo diferencias importan-tes cuando se procedió a comparar los valores enzimáticos entre personas con una enfermedad específica y quienes no la tenían, excepto en el caso de «anemia». CONCLUSIONES: los niveles de colinesterasas eritrocitaria y plasmática son similares entre trabajadores sanos o con enfermedades crónicas controladas, con o sin drogas. PROBLEM: Physiological values of cholinesterase are known in healthy population, but limited information on them is available in individuals with chronic, controlled diseases, either with or without medication. OBJECTIVES: To measure erythrocytic and plasmatic cholinesterase levels in active workers who met the following conditions: to be feeling well and active at their jobs at the time of the study; to suffer from some disease that was under control either with or without medication; not to have been exposed to pesticides based on cholinesterase inhibitors. METHODOLOGY: A survey was carried out among workers affiliated to the Social Security Institute in Antioquia, Colombia, to identify those suffering from some disease and who had it under control. Acetylcholinesterase and butyrylcholinesterase levels were determined using two techniques for the former and three for the latter. Surveyed workers belonged to two different parts of Antioquia, namely: the Aburra Valley and the Near East region. The study sample was made up by 827 persons, 19% of which informed to be suffering from some disease. RESULTS: Prevalence of disease in the Aburra Valley workers was 30% and in those from the Near East region, 9% (p = 0.0000000. The list of their diseases included 13 different ones, the most frequent of which were: hypertension (29%, “liver disease” (16%, anemia (10%, and arthritis (10%. Out of the 827 people, 127 (15% were under some kind of medication at the moment of the study; of them, 85% were being treated with only one drug. Eight per cent were diseased and under

Endothelial cell marker PAL-E reactivity in brain tumor, developing brain, and brain disease

NARCIS (Netherlands)

Leenstra, S.; Troost, D.; Das, P. K.; Claessen, N.; Becker, A. E.; Bosch, D. A.

1993-01-01

The endothelial cell marker PAL-E is not reactive to vessels in the normal brain. The present study concerns the PAL-E reactivity in brain tumors in contrast to normal brain and nonneoplastic brain disease. A total of 122 specimens were examined: brain tumors (n = 94), nonneoplastic brain disease (n

New Direction Treatment in Antidote Treatment of OPC Intoxications

International Nuclear Information System (INIS)

Dishovsky, C.

2007-01-01

The toxic effect of organophosphorus compounds (OPC) is based on inhibition of acetylcholinesterase (AChE), enzyme which plays an important physiological role in the cholinergic nervous system. The drug therapy on intoxication with OPC included mainly combination of cholinesterase reactivators and cholinolytics. There is no single AChE reactivator having the ability to sufficiently reactivate inhibited enzyme due to the high variability of chemical structure of the inhibitors. The classic oximes have antidote effect against intoxication with sarin, Vx and tabun, but are not effective against soman. HI-6 (Bulgarian ampoule form T oxidin ) has an effect against sarin, soman and Vx, and to a lesser degree against tabun. In order to improve the treatment of poisoning with highly toxic OPC, in ours laboratory we synthesized a variety of mono- and dioximes. We use different numbers of pyridinium or heterocyclic rings, different length and shape of the connecting chain between pyridinium or pyridinium-heterocyclic rings; different number and position of the oxime groups at the pyridinium rings and others. The investigations of some authors and our research showed that the compounds which present a combination between HI-6 and TMB-4 have a better antidote activity against tabun intoxications. The important finding of this study is that we synthesized complex compounds, reactivators of cholinesterase activity (including HI-6) with AMP / ATP and polycarboxilats, which have prolonged action in organism compared with original oximes. Pharmacokinetic studies showed that they are eliminated more slowly. The antidotal efficacy of these compounds after soman poisoning in rats was similar like that of the original oximes. The same tendency showed and the other pharmacological (blood pressure, EKG, breathing, neuromuscular transmission), and biochemical (ChE) investigations. (author)

[Application of Bayes Probability Model in Differentiation of Yin and Yang Jaundice Syndromes in Neonates].

Science.gov (United States)

Mu, Chun-sun; Zhang, Ping; Kong, Chun-yan; Li, Yang-ning

2015-09-01

To study the application of Bayes probability model in differentiating yin and yang jaundice syndromes in neonates. Totally 107 jaundice neonates who admitted to hospital within 10 days after birth were assigned to two groups according to syndrome differentiation, 68 in the yang jaundice syndrome group and 39 in the yin jaundice syndrome group. Data collected for neonates were factors related to jaundice before, during and after birth. Blood routines, liver and renal functions, and myocardial enzymes were tested on the admission day or the next day. Logistic regression model and Bayes discriminating analysis were used to screen factors important for yin and yang jaundice syndrome differentiation. Finally, Bayes probability model for yin and yang jaundice syndromes was established and assessed. Factors important for yin and yang jaundice syndrome differentiation screened by Logistic regression model and Bayes discriminating analysis included mothers' age, mother with gestational diabetes mellitus (GDM), gestational age, asphyxia, or ABO hemolytic diseases, red blood cell distribution width (RDW-SD), platelet-large cell ratio (P-LCR), serum direct bilirubin (DBIL), alkaline phosphatase (ALP), cholinesterase (CHE). Bayes discriminating analysis was performed by SPSS to obtain Bayes discriminant function coefficient. Bayes discriminant function was established according to discriminant function coefficients. Yang jaundice syndrome: y1= -21. 701 +2. 589 x mother's age + 1. 037 x GDM-17. 175 x asphyxia + 13. 876 x gestational age + 6. 303 x ABO hemolytic disease + 2.116 x RDW-SD + 0. 831 x DBIL + 0. 012 x ALP + 1. 697 x LCR + 0. 001 x CHE; Yin jaundice syndrome: y2= -33. 511 + 2.991 x mother's age + 3.960 x GDM-12. 877 x asphyxia + 11. 848 x gestational age + 1. 820 x ABO hemolytic disease +2. 231 x RDW-SD +0. 999 x DBIL +0. 023 x ALP +1. 916 x LCR +0. 002 x CHE. Bayes discriminant function was hypothesis tested and got Wilks' λ =0. 393 (P =0. 000). So Bayes

Revisiting Einstein's brain in Brain Awareness Week.

Science.gov (United States)

Chen, Hao; Chen, Su; Zeng, Lidan; Zhou, Lin; Hou, Shengtao

2014-10-01

Albert Einstein's brain has long been an object of fascination to both neuroscience specialists and the general public. However, without records of advanced neuro-imaging of his brain, conclusions regarding Einstein's extraordinary cognitive capabilities can only be drawn based on the unique external features of his brain and through comparison of the external features with those of other human brain samples. The recent discovery of 14 previously unpublished photographs of Einstein's brain taken at unconventional angles by Dr. Thomas Stoltz Harvey, the pathologist, ignited a renewed frenzy about clues to explain Einstein's genius. Dr. Dean Falk and her colleagues, in their landmark paper published in Brain (2013; 136:1304-1327), described in such details about the unusual features of Einstein's brain, which shed new light on Einstein's intelligence. In this article, we ask what are the unique structures of his brain? What can we learn from this new information? Can we really explain his extraordinary cognitive capabilities based on these unique brain structures? We conclude that studying the brain of a remarkable person like Albert Einstein indeed provides us a better example to comprehensively appreciate the relationship between brain structures and advanced cognitive functions. However, caution must be exercised so as not to over-interpret his intelligence solely based on the understanding of the surface structures of his brain.

Plants traditionally used in age-related brain disorders (dementia): an ethanopharmacological survey.

Science.gov (United States)

Natarajan, Suganthy; Shunmugiah, Karutha Pandian; Kasi, Pandima Devi

2013-04-01

Epidemiological studies have shown that despite mortality due to communicable diseases, poverty and human conflicts, the incidence of dementia increases in the developing world in tandem with the ageing population. Although some FDA approved drugs are available for the treatment of dementia, the outcomes are often unsatisfactory. In traditional practices of medicine, numerous plants have been used to treat cognitive disorders, including neurodegenerative diseases such as Alzheimer's disease (AD) and other memory-related disorders. In western medicine most of the drugs used for the treatment of neurodegenerative disorders are derived from plant sources. This article reviews plants and their active constituents that have been used for their reputed cognitive-enhancing and antidementia effects. A literature survey in Science Direct, Pubmed, and Google Scholar was performed to gather information regarding drug discovery from plants sources for the treatment of congnitive disorders and dementia. More than forty herbal remedies were identified with cholinesterase inhibitory, anti-inflammatory, or antioxidant activities. Bioactive compounds include alkaloids, flavonoids, steroids, saponins, terpenoids, and essential oils. About eleven herbal plants with multipotent activity against AD are discussed. Literature surveys show that most of the research has been conducted on herbal remedies effect on cholinesterase inhibitory and antioxidant activities. Studies regarding the effect of herbal drugs on β-secretase inhibitory activity and antiaggregation property are lacking. This review provides leads for identifying potential new drugs from plant sources for the treatment of neurodegenerative disorders.

Fourteen-Day Subchronic Oral Toxicity Study of 4-Nitrophenyl Methyl (Phenyl) Phosphinate in Male and Female Rats.

Science.gov (United States)

1982-09-01

because of concern about the susceptibility of the compound to hydrolysis. If the compound were microencapsulated , one could then mix it with the diet... Enzymatic Activity in Serum...............32 Table 8 - Effect of MPP on Cholinesterase Activity in Plasma ........ 33 Red Blood Cell and Brain I A...4 w) c - U,- APEN I D S C N NC a N Lewis--30 TABLE 7 Egfeat of MPP* on Enzymatic Activity in Serum Aspartate Alanlne Lactate Creatine Amino- Amino

Effects of xenobiotic compounds on the cell activities of Euplotes crassus, a single-cell eukaryotic test organism for the study of the pollution of marine sediments

Energy Technology Data Exchange (ETDEWEB)

Trielli, Francesca [Dipartimento per lo Studio del Territorio e delle sue Risorse, University of Genoa Corso Europa, 26, I-16132 Genova (Italy); Amaroli, Andrea [Dipartimento per lo Studio del Territorio e delle sue Risorse, University of Genoa Corso Europa, 26, I-16132 Genova (Italy); Sifredi, Francesca [Dipartimento per lo Studio del Territorio e delle sue Risorse, University of Genoa Corso Europa, 26, I-16132 Genova (Italy); Marchi, Barbara [Dipartimento di Biologia, University of Genoa, Viale Benedetto XV, 5, I-16132 Genova (Italy); Falugi, Carla [Dipartimento di Biologia, University of Genoa, Viale Benedetto XV, 5, I-16132 Genova (Italy); Corrado, Maria Umberta Delmonte [Dipartimento per lo Studio del Territorio e delle sue Risorse, University of Genoa Corso Europa, 26, I-16132 Genova (Italy)]. E-mail: corrado@dipteris.unige.it

2007-08-01

It is now widely accepted that assays with protists are relevant to be exploited for the study of environmental modifications due to the presence of xenobiotic compounds. In this work, the possibility of utilizing Euplotes crassus, an interstitial marine ciliate, for the pre-chemical screening of estuarine and coastal sediments was evaluated. For this purpose, the effects of exposure to pollutants were tested on the cell viability, fission rate and lysosomal membrane stability of E. crassus. The following toxicants were used: an organophosphate (OP) pesticide, basudin, an organochlorine hydrocarbon, AFD25, both employed especially for pest control in agricultural sites, a toxic heavy metal, mercury (HgCl{sub 2}) and different mixtures of the above-mentioned compounds, as they might occur in polluted sites. Exposure to these toxicants affected cell viability at concentrations ranging from 96.6 to 966 x 10{sup 3} mg/l for basudin, from 3.3 to 33 x 10{sup 3} mg/l for AFD25 and from 0.1 to 1 mg/l for HgCl{sub 2}. A significant decrease in the mean fission rate (P < 0.001) was found after 24- or 48-h exposures to 9.66 mg/l basudin, 3.3 mg/l AFD25 and 7 x 10{sup -2} mg/l HgCl{sub 2}. Furthermore, the Neutral Red Retention Assay showed a significant decrease in lysosomal membrane stability after 60- and 120-min exposures to AFD25 (33 mg/l) and HgCl{sub 2} (0.33 mg/l). In addition, as it is well-known that the inhibition of acetylcholinesterase activity represents a specific biomarker of exposure to OP and carbamate pesticides in higher organisms, initially the presence of cholinesterase (ChE) activity was detected in E. crassus, using cytochemical, spectrophotometric and electrophoretic methods. Afterwards, this enzyme activity was characterized spectrophotometrically by its sensitivity to specific ChE inhibitors and to variations in pH and temperature. The ChE activity was inhibited significantly by basudin- (9.66 and 96.6 mg/l) or AFD25-exposure (3.3 mg/l). Conversely

Quinolinic Carboxylic Acid Derivatives as Potential Multi-target Compounds for Neurodegeneration: Monoamine Oxidase and Cholinesterase Inhibition.

Science.gov (United States)

Khan, Nehal A; Khan, Imtiaz; Abid, Syed M A; Zaib, Sumera; Ibrar, Aliya; Andleeb, Hina; Hameed, Shahid; Iqbal, Jamshed

2018-01-01

Parkinson's disease (PD), a debilitating and progressive disorder, is among the most challenging and devastating neurodegenerative diseases predominantly affecting the people over 60 years of age. To confront PD, an advanced and operational strategy is to design single chemical functionality able to control more than one target instantaneously. In this endeavor, for the exploration of new and efficient inhibitors of Parkinson's disease, we synthesized a series of quinoline carboxylic acids (3a-j) and evaluated their in vitro monoamine oxidase and cholinesterase inhibitory activities. The molecular docking and in silico studies of the most potent inhibitors were performed to identify the probable binding modes in the active site of the monoamine oxidase enzymes. Moreover, molecular properties were calculated to evaluate the druglikeness of the compounds. The biological evaluation results revealed that the tested compounds were highly potent against monoamine oxidase (A & B), 3c targeted both the isoforms of MAO with IC50 values of 0.51 ± 0.12 and 0.51 ± 0.03 µM, respectively. The tested compounds also demonstrated high and completely selective inhibitory action against acetylcholinesterase (AChE) with IC50 values ranging from 4.36 to 89.24 µM. Among the examined derivatives, 3i was recognized as the most potent inhibitor of AChE with an IC50 value of 4.36 ± 0.12 ±µM. The compounds appear to be promising inhibitors and could be used for the future development of drugs targeting neurodegenerative disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Left Brain. Right Brain. Whole Brain

Science.gov (United States)

Farmer, Lesley S. J.

2004-01-01

As the United States student population is becoming more diverse, library media specialists need to find ways to address these distinctive needs. However, some of these differences transcend culture, touching on variations in the brain itself. Most people have a dominant side of the brain, which can affect their personality and learning style.…

Il piu grande centro europeo di ricerca oggi festeggia l'anniversario del Nobel di Rubbia e Van der Meer. Cern, vent'anni guardando al futuro Ora la sfida si gioca sull'acceleratore di particelle pronto per il 2007, che provera a svelare i segreti della materia

CERN Multimedia

Durante, E

2003-01-01

"CERN, vent'anni guardando al futuro Ora la sfida si gioca sull'acceleratore di particelle pronto per il 2007, che provera a svelare i segreti della materia" [CERN, twenty years of looking towards the future. The present challenge is the particle accelerator that will be ready in 2007, which will try to reveal the secrets of matter] (2 pages)

Illustrations to “Gespräche in dem Reiche derer Todten zwischen dem vortreflichen Moscowitischen Czaar Petro Magno und dem grossen Tyrannen Ivan Basilowiz II” (Peter the Great and Ivan the Terrible) by David Fassmann (1725)

OpenAIRE

Ekaterina A. Skvortcova

2017-01-01

The journal created by David Fassmann (1683–1744), Gespräche in dem Reiche derer Todten, edited in Leipzig, was a huge success. Each of the 240 issues presents a dialogue between two historical figures from the afterworld. In the 83rd–86th Entrevuë, the interlocutors are Peter the Great and Ivan the Terrible. The texts of the four conversations were thoroughly examined by Eckhard Matthes (1987). The present paper explores how the illustrations to the 83rd–86th Entrevuë visualize the texts, w...

Structure-Based Design and Optimization of Multitarget-Directed 2H-Chromen-2-one Derivatives as Potent Inhibitors of Monoamine Oxidase B and Cholinesterases.

Science.gov (United States)

Farina, Roberta; Pisani, Leonardo; Catto, Marco; Nicolotti, Orazio; Gadaleta, Domenico; Denora, Nunzio; Soto-Otero, Ramon; Mendez-Alvarez, Estefania; Passos, Carolina S; Muncipinto, Giovanni; Altomare, Cosimo D; Nurisso, Alessandra; Carrupt, Pierre-Alain; Carotti, Angelo

2015-07-23

The multifactorial nature of Alzheimer's disease calls for the development of multitarget agents addressing key pathogenic processes. To this end, by following a docking-assisted hybridization strategy, a number of aminocoumarins were designed, prepared, and tested as monoamine oxidases (MAOs) and acetyl- and butyryl-cholinesterase (AChE and BChE) inhibitors. Highly flexible N-benzyl-N-alkyloxy coumarins 2-12 showed good inhibitory activities at MAO-B, AChE, and BChE but low selectivity. More rigid inhibitors, bearing meta- and para-xylyl linkers, displayed good inhibitory activities and high MAO-B selectivity. Compounds 21, 24, 37, and 39, the last two featuring an improved hydrophilic/lipophilic balance, exhibited excellent activity profiles with nanomolar inhibitory potency toward hMAO-B, high hMAO-B over hMAO-A selectivity and submicromolar potency at hAChE. Cell-based assays of BBB permeation, neurotoxicity, and neuroprotection supported the potential of compound 37 as a BBB-permeant neuroprotective agent against H2O2-induced oxidative stress with poor interaction as P-gp substrate and very low cytotoxicity.

Il Salento che abbiamo attraversato: Rina Durante e Bruno Brancher, il racconto di due vite diverse sulle strade di terra d'Otranto

Directory of Open Access Journals (Sweden)

Massimo Melillo

2015-07-01

Full Text Available Rina Durante ha rappresentato il meglio della cultura meridionale, ne ha raccolto l’eredità e ne è stata tra le interpreti più acute. Abbiamo avuto l’onore della sua amicizia fraterna e solidale, conosciuto l’azzardo e la radicalità delle sue scelte di vita, la sua dolce timidezza e l’ardita padronanza e consapevolezza del suo ruolo: anni di discussioni, di confronto, di legame cementato da infuocati innamoramenti intellettuali per uno scrittore, un poeta, un regista, di accese ironie sui nostri caratteri, di scontri politici e furibondi litigi finiti in un abbraccio. Anche per Bruno Brancher, milanese di tutti e di nessuno, il ricordo si fa memoria per le sue mille improvvise e imprevedibili incursioni in terra salentina. Non era un uomo facile, anche se aveva dalla sua parte il puntiglio dell’innocenza tipica del ladro gentiluomo. Portava leggero il fardello di due vite in una: la prima segnata da una marginalità, fattasi a volte precariamente lussuosa con i proventi di furti e disarmanti rapine; l’altra con la faccia del redento, che con la scoperta della scrittura diventa cosciente di sé.

Dose evaluation for workers employed in an industry involving enamel paints containing zirconium silicate; Valutazione di dose per i lavoratori occupati in una industria che utilizza vernici a smalto contenenti silicato di zirconio

Energy Technology Data Exchange (ETDEWEB)

Castellani, C.M.; Berico, M.; De Zaiacomo, T.; Formignani, M.; Ianni, A.; Nobili, C.; Sandri, S.; Vasselli, R. [ENEA, Centro Ricerche Ezio Clementel, Bologna (Italy). Dipt. Ambiente

1999-07-01

In the frame of the European Recommendations for radiological protection, an evaluation of the annual dose has been made for workers employed in an industry for the production of sanitary equipment involving the use of enamel paints containing zirconium silicate. [Italian] Nella prospettiva dell'applicazione della direttiva europea relativa alla protezione radiologica dei lavoratori, vengono presentati i risultati relativi alla valutazione di dose annuale complessiva per i lavoratori occupati in una industria per la produzione di articoli igienico-sanitari che utilizza vernici a smalto contenenti silicato di zirconio. Il fine e' la valutazione del problema radioprotezionistico per gli addetti a causa delle impurezza radioattive presenti nei materiali utlizzati.

Potential of organic bio processed materials for bioremediation (bio stimulation) of chloropyrifos contaminated soil for food safety

Energy Technology Data Exchange (ETDEWEB)

Kadian, N.; Malik, A.; Satya, S.; Dureja, P.

2009-07-01

Chloropyrifos (CPF), a well-known neutronic agent, causes inhibition of some important enzymes such as acetyl-cholinesterase, ATPase, cholesterol ester-hydrolase. It can pass through the placenta in to the body of fetus and target more on developing brains and new born. Its metabolites are detected in the air, in amniotic fluid and in infant meconium. The inherent persistency of CPF may ensure long-term pest control, but enhances the risk of uptake (by edible plants) and subsequent bioaccumulation. (Author)

Brain Tumors

Science.gov (United States)

A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

Effectiveness of donepezil, rivastigmine, and (+/-)huperzine A in counteracting the acute toxicity of organophosphorus nerve agents: comparison with galantamine.

Science.gov (United States)

Aracava, Yasco; Pereira, Edna F R; Akkerman, Miriam; Adler, Michael; Albuquerque, Edson X

2009-12-01

Galantamine, a centrally acting cholinesterase (ChE) inhibitor and a nicotinic allosteric potentiating ligand used to treat Alzheimer's disease, is an effective and safe antidote against poisoning with nerve agents, including soman. Here, the effectiveness of galantamine was compared with that of the centrally active ChE inhibitors donepezil, rivastigmine, and (+/-)huperzine A as a pre- and/or post-treatment to counteract the acute toxicity of soman. In the first set of experiments, male prepubertal guinea pigs were treated intramuscularly with one of the test drugs and 30 min later challenged with 1.5 x LD(50) soman (42 microg/kg s.c.). All animals that were pretreated with galantamine (6-8 mg/kg), 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A survived the soman challenge, provided that they were also post-treated with atropine (10 mg/kg i.m.). However, only galantamine was well tolerated. In subsequent experiments, the effectiveness of specific treatment regimens using 8 mg/kg galantamine, 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A was compared in guinea pigs challenged with soman. In the absence of atropine, only galantamine worked as an effective and safe pretreatment in animals challenged with 1.0 x LD(50) soman. Galantamine was also the only drug to afford significant protection when given to guinea pigs after 1.0 x LD(50) soman. Finally, all test drugs except galantamine reduced the survival of the animals when administered 1 or 3 h after the challenge with 0.6 or 0.7 x LD(50) soman. Thus, galantamine emerges as a superior antidotal therapy against the toxicity of soman.

Brain anatomical networks in early human brain development.

Science.gov (United States)

Fan, Yong; Shi, Feng; Smith, Jeffrey Keith; Lin, Weili; Gilmore, John H; Shen, Dinggang

2011-02-01

Recent neuroimaging studies have demonstrated that human brain networks have economic small-world topology and modular organization, enabling efficient information transfer among brain regions. However, it remains largely unknown how the small-world topology and modular organization of human brain networks emerge and develop. Using longitudinal MRI data of 28 healthy pediatric subjects, collected at their ages of 1 month, 1 year, and 2 years, we analyzed development patterns of brain anatomical networks derived from morphological correlations of brain regional volumes. The results show that the brain network of 1-month-olds has the characteristically economic small-world topology and nonrandom modular organization. The network's cost efficiency increases with the brain development to 1 year and 2 years, so does the modularity, providing supportive evidence for the hypothesis that the small-world topology and the modular organization of brain networks are established during early brain development to support rapid synchronization and information transfer with minimal rewiring cost, as well as to balance between local processing and global integration of information. Copyright © 2010. Published by Elsevier Inc.

Review of UV spectroscopic, chromatographic, and electrophoretic methods for the cholinesterase reactivating antidote pralidoxime (2-PAM).

Science.gov (United States)

John, Harald; Blum, Marc-Michael

2012-01-01

Pralidoxime (2-PAM) belongs to the class of monopyridinium oximes with reactivating potency on cholinesterases inhibited by phosphylating organophosphorus compounds (OPC), for example, pesticides and nerve agents. 2-PAM represents an established antidote for the therapy of anticholinesterase poisoning since the late 1950s. Quite high therapeutic concentrations in human plasma (about 13 µg/ml) lead to concentrations in urine being about 100 times higher allowing the use of less sensitive analytical techniques that were used especially in the early years after 2-PAM was introduced. In this time (mid-1950s until the end of the 1970s) 2-PAM was most often analyzed by either paper chromatography or simple UV spectroscopic techniques omitting any sample separation step. These methods were displaced completely after the establishment of column liquid chromatography in the early 1980s. Since then, diverse techniques including cation exchange, size-exclusion, reversed-phase, and ligand-exchange chromatography have been introduced. Today, the most popular method for 2-PAM quantification is ion pair chromatography often combined with UV detection representing more than 50% of all column chromatographic procedures published. Furthermore, electrophoretic approaches by paper and capillary zone electrophoresis have been successfully used but are seldom applied. This review provides a commentary and exhaustive summary of analytical techniques applied to detect 2-PAM in pharmaceutical formulations and biological samples to characterize stability and pharmacokinetics as well as decomposition and biotransformation products. Separation techniques as well as diverse detectors are discussed in appropriate detail allowing comparison of individual preferences and limitations. In addition, novel data on mass spectrometric fragmentation of 2-PAM are provided. Copyright © 2011 John Wiley & Sons, Ltd.

Does the cholinesterase inhibitor, donepezil, benefit both declarative and non-declarative processes in mild to moderate Alzheimer's disease?

Science.gov (United States)

Winstein, Carolee J; Bentzen, Kirk R; Boyd, Lara; Schneider, Lon S

2007-07-01

Previous research suggests separate neural networks for implicit (non-declarative) and explicit (declarative) memory processes. A core cognitive impairment in mild to moderate Alzheimer's disease (AD) is a pronounced declarative memory and learning deficit with relative preservation of non-declarative memory. Cholinesterase inhibitors has been purported to enhance cognitive function, and previous clinical trials consistently showed that donepezil, a reversible inhibitor of acetylcholinesterase (AChE), led to statistically significant improvements in cognition and patient function. This prospective pilot study is a randomized, double blind, placebo-controlled clinical trial investigating 10 patients with AD. Our purpose was to examine the relationship between declarative and non-declarative capability with particular emphasis on implicit sequence learning. Patients were assessed at baseline and again at 4-weeks. After participants' baseline data were obtained, each was double-blindly randomized to one of two groups: donepezil or placebo. At baseline participants were tested with two outcome measures (Serial Reaction Time Task, Alzheimer's Disease Assessment Scale-Cognitive Subscale). Participants were given either 5 mg donepezil or an identically appearing placebo to be taken nightly for 4 weeks (28 tablets), and then retested. The donepezil group demonstrated a greater likelihood of increases in both non-declarative and declarative processes. The placebo group was mixed without clearly definable trends or patterns. When the data were examined for coincidental changes in the two outcome measures together they are suggestive of a benefit from donepezil treatment for non-declarative and declarative processes.

Brain edema associated with unruptured brain arteriovenous malformations

International Nuclear Information System (INIS)

Kim, Bum-soo; Sarma, Dipanka; Lee, Seon-Kyu; ter Brugge, Karel G.

2009-01-01

Brain edema in unruptured brain arteriovenous malformations (AVMs) is rare; this study examines (1) its frequency and clinical presentation, (2) imaging findings with emphasis on venous drainage abnormalities, and (3) implications of these findings on natural history and management. Presentation and imaging features of all unruptured brain AVMs were prospectively collected in our brain AVM database. Neurological findings, size, location, venous drainage pattern, presence of venous thrombosis, ectasia, or stenosis, and brain edema were specifically recorded. Treatment details of all patients with brain edema and their clinical and imaging follow-up were reviewed. Finally, a comparison was made between patients with and without edema. Brain edema was found in 13/329 unruptured brain AVMs (3.9%). Neurological deficit (46.2%), venous thrombosis (38.5%), venous ectasia (84.6%), stenosis (38.5%), and contrast stagnation in the draining veins (84.6%) were more frequent in patients with brain edema than without edema. Eight patients with brain edema received specific treatment (embolization = 5, surgery = 2, radiosurgery = 1). Clinical features correlated well with change in degree of edema in six. Three of five embolized patients were stable or showed improvement after the procedure. On follow-up, however, intracranial hemorrhage developed in three. Brain edema in unruptured brain AVMs is rare, 3.9% in this series. Venous outflow abnormalities are frequently associated and appear to contribute to the development of edema. Progressive nonhemorrhagic symptoms are also associated, with a possible increased risk of hemorrhage. Palliative embolization arrests the nonhemorrhagic symptoms in selected patients, although it may not have an effect on hemorrhagic risk. (orig.)

Synthesis of Selective Butyrylcholinesterase Inhibitors Coupled between α-Lipoic Acid and Polyphenols by Using 2-(Piperazin-1-yl)ethanol Linker

International Nuclear Information System (INIS)

Yeun, Go Heun; Lee, Seung Hwan; LIm, Yong Bae; Lee, Hye Sook; Lee, Bong Ho; Park, Jeong Ho; Won, Mooho

2013-01-01

In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between α-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The IC 50 values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE (IC 50 = 0.44 ± 0.24 μM). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is 4.3 ± 0.09 μM

Synthesis of Selective Butyrylcholinesterase Inhibitors Coupled between α-Lipoic Acid and Polyphenols by Using 2-(Piperazin-1-yl)ethanol Linker

Energy Technology Data Exchange (ETDEWEB)

Yeun, Go Heun; Lee, Seung Hwan; LIm, Yong Bae; Lee, Hye Sook; Lee, Bong Ho; Park, Jeong Ho [Hanbat National Univ., Daejeon (Korea, Republic of); Won, Mooho [Kangwon National Univ., Chuncheon (Korea, Republic of)

2013-04-15

In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between α-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The IC{sub 50} values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE (IC{sub 50} = 0.44 ± 0.24 μM). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is 4.3 ± 0.09 μM.

What will this do to me and my brain? Ethical issues in brain-to-brain interfacing

Directory of Open Access Journals (Sweden)

Elisabeth eHildt

2015-02-01

Full Text Available For several years now, brain-computer interfaces (BCIs in which brain signals are used to navigate a computer, a prostheses or a technical device, have been developed in various experimental contexts (Wolpaw & Wolpaw 2012; Grübler & Hildt 2014. Researchers have recently taken the next step and run experiments based on connections between two brains. These so-called brain-to-brain interfaces (abbreviation: BBIs or BTBIs involve not only a BCI component deriving information from a brain and sending it to a computer, but also a computer-brain interface (CBI component delivering information to another brain. What results is technology-mediated brain-to-brain communication (B2B communication, i.e. direct communication between two brains that does not involve any activity of the peripheral nervous system. In what follows, ethical issues that arise in neural interfacing will be discussed after a short introduction to recent BBI experiments. In this, the focus will be on the implications BBIs may have on the individual at the CBI side of the BBI, i.e. on the recipient.

Brain-machine and brain-computer interfaces.

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Friehs, Gerhard M; Zerris, Vasilios A; Ojakangas, Catherine L; Fellows, Mathew R; Donoghue, John P

2004-11-01

The idea of connecting the human brain to a computer or machine directly is not novel and its potential has been explored in science fiction. With the rapid advances in the areas of information technology, miniaturization and neurosciences there has been a surge of interest in turning fiction into reality. In this paper the authors review the current state-of-the-art of brain-computer and brain-machine interfaces including neuroprostheses. The general principles and requirements to produce a successful connection between human and artificial intelligence are outlined and the authors' preliminary experience with a prototype brain-computer interface is reported.

FROM BRAIN DRAIN TO BRAIN NETWORKING

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Irina BONCEA

2015-06-01

Full Text Available Scientific networking is the most accessible way a country can turn the brain drain into brain gain. Diaspora’s members offer valuable information, advice or financial support from the destination country, without being necessary to return. This article aims to investigate Romania’s potential of turning brain drain into brain networking, using evidence from the medical sector. The main factors influencing the collaboration with the country of origin are investigated. The conclusions suggest that Romania could benefit from the diaspora option, through an active implication at institutional level and the implementation of a strategy in this area.