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

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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.
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
Two Fatal Intoxications Involving Butyryl Fentanyl

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Poklis, Justin; Poklis, Alphonse; Wolf, Carl; Hathaway, Cindie; Arbefeville, Elise; Chrostowski, Leszek; Devers, Kelly; Hair, Laura; Mainland, Mary; Merves, Michele; Pearson, Julia

2016-01-01

We present the case histories, autopsy findings and toxicology findings of two fatal intoxications involving the designer drug, butyryl fentanyl. The quantitative analysis of butyryl fentanyl in postmortem fluids and tissues was performed by an ultrahigh-performance liquid chromatography tandem mass spectrometry method. In the first case, butyryl fentanyl was the only drug detected with concentrations of 99 ng/mL in peripheral blood, 220 ng/mL in heart blood, 32 ng/mL in vitreous humor, 590 ng/mL in gastric contents, 93 ng/g in brain, 41 ng/g in liver, 260 ng/mL in bile and 64 ng/mL in urine. The cause of death was ruled fatal intoxication by butyryl fentanyl. In the second case, butyryl fentanyl was detected along with acetyl fentanyl, alprazolam and ethanol. The butyryl fentanyl concentrations were 3.7 ng/mL in peripheral blood, 9.2 ng/mL in heart blood, 9.8 ng/mL in vitreous humor, 4,000 ng/mL in gastric contents, 63 ng/g in brain, 39 ng/g in liver, 49 ng/mL in bile and 2 ng/mL in urine. The acetyl fentanyl concentrations were 21 ng/mL in peripheral blood, 95 ng/mL in heart blood, 68 ng/mL in vitreous humor, 28,000 ng/mL in gastric contents, 200 ng/g in brain, 160 ng/g in liver, 330 ng/mL in bile and 8 ng/mL in urine. In addition, the alprazolam concentration was 40 ng/mL and the ethanol concentration was 0.11 g/dL, both measured in peripheral blood. The cause of death in the second case was ruled a mixed drug intoxication. In both cases, the manner of death was accident. PMID:27339481
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
Multitarget-directed tricyclic pyridazinones as G protein-coupled receptor ligands and cholinesterase inhibitors.

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

Directory of Open Access Journals (Sweden)

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
Enzyme Inhibitory and Molecular Docking Studies on Some Organic Molecules of Natural Occurrence

International Nuclear Information System (INIS)

Abbasi, M. A.; Hussain, G.; Rehman, A. U.; Shahwar, D.; Mohyuddin, A.; Ashraf, M.; Rahman, J.; Lodhi, M. A.; Khan, F. A.

2016-01-01

In the present study, in vitro enzyme inhibitory studies on cinchonidine (1), cinchonine (2), quinine (3), noscapine (narcotine, 4) and santonine (5) were carried out. The various enzymes included in the study were lipoxygenase, xanthine oxidase, acetyl cholinesterase, butyryl cholinesterase and protease. The results revealed that 2, 3, and 4 were moderate active against lipoxygenase and xanthine oxidase enzymes. The molecule 3 possessed weak activity against butyryl cholinesterase enzyme while remaining molecules were inactive against this enzyme. However, all these compounds were inactive against acetyl cholinestrase and protease enzymes. The synthesized compounds were computationally docked into the active site of lipoxygenase enzyme. The compounds 3 and 4 showed decent interactions, hence strengthening the observed results. (author)
Genetic screening in the Persian Jewish community: A pilot study.

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Kaback, Michael; Lopatequi, Jean; Portuges, Amin Riley; Quindipan, Cathy; Pariani, Mitchel; Salimpour-Davidov, Nilou; Rimoin, David L

2010-10-01

Israeli investigators have identified several relatively frequent disorders due to founder point mutations in Persian (Iranian) Jews, who, for nearly three centuries up to the Islamic Revolution of 1979, were completely isolated reproductively. Using a community-based model previously employed with Tay-Sachs disease prevention, we developed a pilot program for the Persian Jewish community of greater Los Angeles. We screened for mutations responsible for four relatively frequent autosomal recessive conditions in Persian Jews in which effective interventions are available for each: Pseudocholinesterase deficiency (butyryl cholinesterase deficiency); Congenital hypoaldosteronism (corticosterone methyl oxidase II); Autoimmune polyendocrinopathy (autoimmune regulatory element); and Hereditary Inclusion Body myopathy. One thousand individuals volunteered. Mutations were assessed in saliva-derived DNA and were positive for 121/1000 butyryl cholinesterase deficiency; 92/1000 Hereditary Inclusion Body myopathy; 38/1000 corticosterone methyl oxidase II; and 37/1000 autoimmune regulatory element. Ten homozygous individuals (9 butyryl cholinesterase deficiency and 1 Hereditary Inclusion Body myopathy) and 10 "at-risk" couples (seven for butyryl cholinesterase deficiency and one each for the other three disorders) were identified. These frequencies are comparable with those in Israel and indicate an extraordinary level of inbreeding, as anticipated. A carefully planned effort can be delivered to an "increased risk" community if detailed attention is given to planning and organization. However, availability of an effective intervention for those found to be "at-risk" or possibly affected, is essential before embarking.
Synthesis, pharmacology and molecular docking on multifunctional tacrine-ferulic acid hybrids as cholinesterase inhibitors against Alzheimer's disease.

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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.
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
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.
Coupled ferredoxin and crotonyl coenzyme A (CoA) reduction with NADH catalyzed by the butyryl-CoA dehydrogenase/Etf complex from Clostridium kluyveri.

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Li, Fuli; Hinderberger, Julia; Seedorf, Henning; Zhang, Jin; Buckel, Wolfgang; Thauer, Rudolf K

2008-02-01

Cell extracts of butyrate-forming clostridia have been shown to catalyze acetyl-coenzyme A (acetyl-CoA)- and ferredoxin-dependent formation of H2 from NADH. It has been proposed that these bacteria contain an NADH:ferredoxin oxidoreductase which is allosterically regulated by acetyl-CoA. We report here that ferredoxin reduction with NADH in cell extracts from Clostridium kluyveri is catalyzed by the butyryl-CoA dehydrogenase/Etf complex and that the acetyl-CoA dependence previously observed is due to the fact that the cell extracts catalyze the reduction of acetyl-CoA with NADH via crotonyl-CoA to butyryl-CoA. The cytoplasmic butyryl-CoA dehydrogenase complex was purified and is shown to couple the endergonic reduction of ferredoxin (E0' = -410 mV) with NADH (E0' = -320 mV) to the exergonic reduction of crotonyl-CoA to butyryl-CoA (E0' = -10 mV) with NADH. The stoichiometry of the fully coupled reaction is extrapolated to be as follows: 2 NADH + 1 oxidized ferredoxin + 1 crotonyl-CoA = 2 NAD+ + 1 ferredoxin reduced by two electrons + 1 butyryl-CoA. The implications of this finding for the energy metabolism of butyrate-forming anaerobes are discussed in the accompanying paper.
Coupled Ferredoxin and Crotonyl Coenzyme A (CoA) Reduction with NADH Catalyzed by the Butyryl-CoA Dehydrogenase/Etf Complex from Clostridium kluyveri▿ †

Science.gov (United States)

Li, Fuli; Hinderberger, Julia; Seedorf, Henning; Zhang, Jin; Buckel, Wolfgang; Thauer, Rudolf K.

2008-01-01

Cell extracts of butyrate-forming clostridia have been shown to catalyze acetyl-coenzyme A (acetyl-CoA)- and ferredoxin-dependent formation of H2 from NADH. It has been proposed that these bacteria contain an NADH:ferredoxin oxidoreductase which is allosterically regulated by acetyl-CoA. We report here that ferredoxin reduction with NADH in cell extracts from Clostridium kluyveri is catalyzed by the butyryl-CoA dehydrogenase/Etf complex and that the acetyl-CoA dependence previously observed is due to the fact that the cell extracts catalyze the reduction of acetyl-CoA with NADH via crotonyl-CoA to butyryl-CoA. The cytoplasmic butyryl-CoA dehydrogenase complex was purified and is shown to couple the endergonic reduction of ferredoxin (E0′ = −410 mV) with NADH (E0′ = −320 mV) to the exergonic reduction of crotonyl-CoA to butyryl-CoA (E0′ = −10 mV) with NADH. The stoichiometry of the fully coupled reaction is extrapolated to be as follows: 2 NADH + 1 oxidized ferredoxin + 1 crotonyl-CoA = 2 NAD+ + 1 ferredoxin reduced by two electrons + 1 butyryl-CoA. The implications of this finding for the energy metabolism of butyrate-forming anaerobes are discussed in the accompanying paper. PMID:17993531
Biological, chemical and in silico fingerprints of Dianthus calocephalus Boiss.: A novel source for rutin.

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Uysal, Sengul; Aktumsek, Abdurrahman; Picot-Allain, Carene M N; Unuvar, Hamiyet; Mollica, Adriano; Georgiev, Milen I; Zengin, Gokhan; Mahomoodally, Mohamad Fawzi

2018-03-01

Extracts (methanol, ethyl acetate, and water) from Dianthus calocephalus Boiss. prepared by different extraction techniques (maceration, Soxhlet, and ultrasonication) were studied for possible inhibitory action against key enzymes (α-amylase, α-glucosidase, acetyl cholinesterase, butyryl cholinesterase, and tyrosinase). Antioxidant potential was established using a battery of assays and phenolic compounds profiled by RP-HPLC. Binding pose of tyrosinase with rutin was studied by means of molecular docking. Methanol extracts showed the highest phenolic (39.35-40.25 mgGAE/g) content and rich in rutin (61.38-72.07 mg/g extract). Ethyl acetate extracts of D. calocephalus were potent inhibitors of acetyl (1.45-1.48 mgGALAE/g) and butyryl (2.44-2.74 mgGALAE/g) cholinesterases. Docking studies showed that rutin interacts with the side chains of the key amino acid residues and to the copper atom found at the active site of tyrosinase. Methanol extracts showed highest antioxidant capacity. D. calocephalus showed interesting biological properties that could be further studied to manage diabetes, neurodegenerative diseases, Alzheimer's disease, and hyperpigmentation. Copyright © 2018 Elsevier Ltd. All rights reserved.
Persistent increase of plasma butyryl/isobutyrylcarnitine concentrations as marker of SCAD defect and ethylmalonic encephalopathy

DEFF Research Database (Denmark)

Merinero, B; Perez-Cerda, C; Ruiz Sala, P

2007-01-01

High concentrations of butyryl/isobutyrylcarnitine (C(4)-carnitine) in plasma with increase of ethylmalonic acid (EMA) in urine point to different genetic entities, and further investigations are required to differentiate the possible underlying defect. Here we report three unrelated cases, two n...
Cholinesterase-based biosensors.

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

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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.
[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.

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.

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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.
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.
Anticholinesterase constituents from the leaves of Spondias mombin L. (Anacardiaceae

Directory of Open Access Journals (Sweden)

Elufioye TO

2017-08-01

Full Text Available Taiwo Olayemi Elufioye,1 Efere M Obuotor,2 Joseph M Agbedahunsi,3 Saburi A Adesanya4 1Department of Pharmacognosy, Faculty of Pharmacy, University of Ibadan, Ibadan, 2Department of Biochemistry, 3Drug Research and Production Unit, Faculty of Pharmacy, 4Department of Pharmacognosy, Faculty of Pharmacy, Obafemi Awolowo University, Ile Ife, Osun, Nigeria Abstract: Spondias mombin has been used in traditional medicine for the management of several diseases, including memory loss. This study aimed to evaluate the cholinesterase inhibitory activity of the methanol extract of the leaves and its derived fractions, as well as carry out detailed phytochemical investigations leading to the isolation and characterization of bioactive compounds from the plant. The acetyl cholinesterase (AChE and butyryl cholinesterase (BUChE inhibitory activities were evaluated by colorimetric and thin-layer chromatography bioautographic assay techniques. The ethyl acetate fraction was most active against both enzymes, with percentage inhibition of 58.10 ± 1.08% and 52.66 ± 1.34% against AChE and BUChE, respectively. Three compounds, namely, botulin, campesterol and phytol, with IC50 of 0.88 μg/mL (AChE, 4.67 μg/mL (BuChE; 1.89 μg/mL (AChE, 4.08 μg/mL (BuChE and 12.51 μg/mL (AChE, 23.89 μg/mL (BuChE, respectively, were isolated from the supernatant of the ethyl acetate fraction. The isolated cholinesterase inhibitory compounds correlate with the known memory-enhancing property of the plant and thus support one of its uses in ethnomedicine. Keywords: Alzheimer’s disease, acetylcholinesterase, butyryl cholinesterase, neurodegenerative, Spondias mombin
Brain cDNA clone for human cholinesterase

International Nuclear Information System (INIS)

McTiernan, C.; Adkins, S.; Chatonnet, A.; Vaughan, T.A.; Bartels, C.F.; Kott, M.; Rosenberry, T.L.; La Du, B.N.; Lockridge, O.

1987-01-01

A cDNA library from human basal ganglia was screened with oligonucleotide probes corresponding to portions of the amino acid sequence of human serum cholinesterase. Five overlapping clones, representing 2.4 kilobases, were isolated. The sequenced cDNA contained 207 base pairs of coding sequence 5' to the amino terminus of the mature protein in which there were four ATG translation start sites in the same reading frame as the protein. Only the ATG coding for Met-(-28) lay within a favorable consensus sequence for functional initiators. There were 1722 base pairs of coding sequence corresponding to the protein found circulating in human serum. The amino acid sequence deduced from the cDNA exactly matched the 574 amino acid sequence of human serum cholinesterase, as previously determined by Edman degradation. Therefore, our clones represented cholinesterase rather than acetylcholinesterase. It was concluded that the amino acid sequences of cholinesterase from two different tissues, human brain and human serum, were identical. Hybridization of genomic DNA blots suggested that a single gene, or very few genes coded for cholinesterase
Phosalone-Induced Changes in Regional Cholinesterase Activities ...

African Journals Online (AJOL)

... in Regional Cholinesterase Activities in Rat Brain during Behavioral Tolerance. ... lead to the gradual disappearance of the initial signs of toxicity over time, termed ... regions, striatum recorded a greater decrease in cholinesterase activity.
Function and phylogeny of bacterial butyryl-CoA:acetate transferases and their diversity in the proximal colon of swine

Science.gov (United States)

Studying the host-associated butyrate-producing bacterial community is important because butyrate is essential for colonic homeostasis and gut health. Previous research has identified the butyryl-coA:acetate transferase (2.3.8.3) as a the main gene for butyrate production in intestinal ecosystems; h...
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
Studies on the mechanism of electron bifurcation catalyzed by electron transferring flavoprotein (Etf) and butyryl-CoA dehydrogenase (Bcd) of Acidaminococcus fermentans.

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Chowdhury, Nilanjan Pal; Mowafy, Amr M; Demmer, Julius K; Upadhyay, Vikrant; Koelzer, Sebastian; Jayamani, Elamparithi; Kahnt, Joerg; Hornung, Marco; Demmer, Ulrike; Ermler, Ulrich; Buckel, Wolfgang

2014-02-21

Electron bifurcation is a fundamental strategy of energy coupling originally discovered in the Q-cycle of many organisms. Recently a flavin-based electron bifurcation has been detected in anaerobes, first in clostridia and later in acetogens and methanogens. It enables anaerobic bacteria and archaea to reduce the low-potential [4Fe-4S] clusters of ferredoxin, which increases the efficiency of the substrate level and electron transport phosphorylations. Here we characterize the bifurcating electron transferring flavoprotein (EtfAf) and butyryl-CoA dehydrogenase (BcdAf) of Acidaminococcus fermentans, which couple the exergonic reduction of crotonyl-CoA to butyryl-CoA to the endergonic reduction of ferredoxin both with NADH. EtfAf contains one FAD (α-FAD) in subunit α and a second FAD (β-FAD) in subunit β. The distance between the two isoalloxazine rings is 18 Å. The EtfAf-NAD(+) complex structure revealed β-FAD as acceptor of the hydride of NADH. The formed β-FADH(-) is considered as the bifurcating electron donor. As a result of a domain movement, α-FAD is able to approach β-FADH(-) by about 4 Å and to take up one electron yielding a stable anionic semiquinone, α-FAD, which donates this electron further to Dh-FAD of BcdAf after a second domain movement. The remaining non-stabilized neutral semiquinone, β-FADH(•), immediately reduces ferredoxin. Repetition of this process affords a second reduced ferredoxin and Dh-FADH(-) that converts crotonyl-CoA to butyryl-CoA.
Cholinesterase modulations in patients with acute bacterial meningitis

DEFF Research Database (Denmark)

Berg, Ronan M G; Ofek, Keren; Qvist, Tavs

2011-01-01

The circulating cholinesterases acetyl- and butyrylcholinesterase may be suppressed and subsequently released from the brain in acute bacterial meningitis.......The circulating cholinesterases acetyl- and butyrylcholinesterase may be suppressed and subsequently released from the brain in acute bacterial meningitis....
Studies on the Mechanism of Electron Bifurcation Catalyzed by Electron Transferring Flavoprotein (Etf) and Butyryl-CoA Dehydrogenase (Bcd) of Acidaminococcus fermentans*

Science.gov (United States)

Chowdhury, Nilanjan Pal; Mowafy, Amr M.; Demmer, Julius K.; Upadhyay, Vikrant; Koelzer, Sebastian; Jayamani, Elamparithi; Kahnt, Joerg; Hornung, Marco; Demmer, Ulrike; Ermler, Ulrich; Buckel, Wolfgang

2014-01-01

Electron bifurcation is a fundamental strategy of energy coupling originally discovered in the Q-cycle of many organisms. Recently a flavin-based electron bifurcation has been detected in anaerobes, first in clostridia and later in acetogens and methanogens. It enables anaerobic bacteria and archaea to reduce the low-potential [4Fe-4S] clusters of ferredoxin, which increases the efficiency of the substrate level and electron transport phosphorylations. Here we characterize the bifurcating electron transferring flavoprotein (EtfAf) and butyryl-CoA dehydrogenase (BcdAf) of Acidaminococcus fermentans, which couple the exergonic reduction of crotonyl-CoA to butyryl-CoA to the endergonic reduction of ferredoxin both with NADH. EtfAf contains one FAD (α-FAD) in subunit α and a second FAD (β-FAD) in subunit β. The distance between the two isoalloxazine rings is 18 Å. The EtfAf-NAD+ complex structure revealed β-FAD as acceptor of the hydride of NADH. The formed β-FADH− is considered as the bifurcating electron donor. As a result of a domain movement, α-FAD is able to approach β-FADH− by about 4 Å and to take up one electron yielding a stable anionic semiquinone, α-FAD⨪, which donates this electron further to Dh-FAD of BcdAf after a second domain movement. The remaining non-stabilized neutral semiquinone, β-FADH•, immediately reduces ferredoxin. Repetition of this process affords a second reduced ferredoxin and Dh-FADH− that converts crotonyl-CoA to butyryl-CoA. PMID:24379410
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
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...
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...
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.
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.
(-)-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.
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.
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.
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.

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.
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)
Monitoring of plasma butyrylcholinesterase activity and hematological parameters in pesticide sprayers

OpenAIRE

Rastogi, S. K.; Singh, Vipul K.; Kesavachandran, C.; Jyoti,; Siddiqui, M. K. J.; Mathur, N.; Bharti, R. S.

2008-01-01

To evaluate the health impact of spraying organophosphorus insecticides (OPs), 34 male sprayers in the mango belt of Malihabad, a small town located 27 km from Lucknow in North India was selected. Plasma butyryl cholinesterase (PBChE) and complete blood count were assessed among sprayers after spraying pesticides and the findings obtained were compared with those determined in a reference group ( n = 18). The most common symptoms observed were burning sensation in the eyes (8.82%), it...
Assessment of serum level cholinesterase as a biomarker of liver cirrhosis in Egyptian cirrhotic patients

Directory of Open Access Journals (Sweden)

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

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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.
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.
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. ...
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.
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].

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

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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 ...
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.)
Coumarins as cholinesterase inhibitors: A review.

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

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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

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

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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

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.

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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.
[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
Regional cholinesterase activity in white-throated sparrow brain is differentially affected by acephate (Orthene®)

Science.gov (United States)

Vyas, N.B.; Kuenzel, W.J.; Hill, E.F.; Romo, G.A.; Komaragiri, M.V.S.

1996-01-01

Effects of a 14-day dietary exposure to an organophosphorus pesticide, acephate (acetylphosphoramidothioic acid O,S-dimethyl ester), were determined on cholinesterase activity in three regions (basal ganglia, hippocampus, and hypothalamus) of the white-throated sparrow, Zonotrichia albicollis, brain. All three regions experienced depressed cholinesterase activity between 0.5–2 ppm acephate. The regions exhibited cholinesterase recovery at 2–16 ppm acephate; however, cholinesterase activity dropped and showed no recovery at higher dietary levels (>16 ppm acephate). Evidence indicates that the recovery is initiated by the magnitude of depression, not the duration. In general, as acephate concentration increased, differences in ChE activity among brain regions decreased. Three terms are introduced to describe ChE response to acephate exposure: 1) ChE resistance threshold, 2) ChE compensation threshold, and 3) ChE depression threshold. It is hypothesized that adverse effects to birds in the field may occur at pesticide exposure levels customarily considered negligible.
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.
Structural snapshots along the reaction pathway of Yersinia pestis RipA, a putative butyryl-CoA transferase

International Nuclear Information System (INIS)

Torres, Rodrigo; Lan, Benson; Latif, Yama; Chim, Nicholas; Goulding, Celia W.

2014-01-01

The crystal structures of Y. pestis RipA mutants were determined to provide insights into the CoA transferase reaction pathway. Yersinia pestis, the causative agent of bubonic plague, is able to survive in both extracellular and intracellular environments within the human host, although its intracellular survival within macrophages is poorly understood. A novel Y. pestis three-gene rip (required for intracellular proliferation) operon, and in particular ripA, has been shown to be essential for survival and replication in interferon γ-induced macrophages. RipA was previously characterized as a putative butyryl-CoA transferase proposed to yield butyrate, a known anti-inflammatory shown to lower macrophage-produced NO levels. RipA belongs to the family I CoA transferases, which share structural homology, a conserved catalytic glutamate which forms a covalent CoA-thioester intermediate and a flexible loop adjacent to the active site known as the G(V/I)G loop. Here, functional and structural analyses of several RipA mutants are presented in an effort to dissect the CoA transferase mechanism of RipA. In particular, E61V, M31G and F60M RipA mutants show increased butyryl-CoA transferase activities when compared with wild-type RipA. Furthermore, the X-ray crystal structures of E61V, M31G and F60M RipA mutants, when compared with the wild-type RipA structure, reveal important conformational changes orchestrated by a conserved acyl-group binding-pocket phenylalanine, Phe85, and the G(V/I)G loop. Binary structures of M31G RipA and F60M RipA with two distinct CoA substrate conformations are also presented. Taken together, these data provide CoA transferase reaction snapshots of an open apo RipA, a closed glutamyl-anhydride intermediate and an open CoA-thioester intermediate. Furthermore, biochemical analyses support essential roles for both the catalytic glutamate and the flexible G(V/I)G loop along the reaction pathway, although further research is required to fully
Structural snapshots along the reaction pathway of Yersinia pestis RipA, a putative butyryl-CoA transferase

Energy Technology Data Exchange (ETDEWEB)

Torres, Rodrigo; Lan, Benson; Latif, Yama; Chim, Nicholas [UC Irvine, 2212 Natural Sciences I, Irvine, CA 92697 (United States); Goulding, Celia W., E-mail: celia.goulding@uci.edu [UC Irvine, 2212 Natural Sciences I, Irvine, CA 92697 (United States); UC Irvine, 2302 Natural Sciences I, Irvine, CA 92697 (United States)

2014-04-01

The crystal structures of Y. pestis RipA mutants were determined to provide insights into the CoA transferase reaction pathway. Yersinia pestis, the causative agent of bubonic plague, is able to survive in both extracellular and intracellular environments within the human host, although its intracellular survival within macrophages is poorly understood. A novel Y. pestis three-gene rip (required for intracellular proliferation) operon, and in particular ripA, has been shown to be essential for survival and replication in interferon γ-induced macrophages. RipA was previously characterized as a putative butyryl-CoA transferase proposed to yield butyrate, a known anti-inflammatory shown to lower macrophage-produced NO levels. RipA belongs to the family I CoA transferases, which share structural homology, a conserved catalytic glutamate which forms a covalent CoA-thioester intermediate and a flexible loop adjacent to the active site known as the G(V/I)G loop. Here, functional and structural analyses of several RipA mutants are presented in an effort to dissect the CoA transferase mechanism of RipA. In particular, E61V, M31G and F60M RipA mutants show increased butyryl-CoA transferase activities when compared with wild-type RipA. Furthermore, the X-ray crystal structures of E61V, M31G and F60M RipA mutants, when compared with the wild-type RipA structure, reveal important conformational changes orchestrated by a conserved acyl-group binding-pocket phenylalanine, Phe85, and the G(V/I)G loop. Binary structures of M31G RipA and F60M RipA with two distinct CoA substrate conformations are also presented. Taken together, these data provide CoA transferase reaction snapshots of an open apo RipA, a closed glutamyl-anhydride intermediate and an open CoA-thioester intermediate. Furthermore, biochemical analyses support essential roles for both the catalytic glutamate and the flexible G(V/I)G loop along the reaction pathway, although further research is required to fully
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
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.
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).
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...
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 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.
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.
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.
[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

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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
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
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.
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
[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.
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
Characterization of cholinesterases in plasma of three Portuguese native bird species: application to biomonitoring.

Directory of Open Access Journals (Sweden)

Cátia S A Santos

Full Text Available Over the last decades the inhibition of plasma cholinesterase (ChE activity has been widely used as a biomarker to diagnose organophosphate and carbamate exposure. Plasma ChE activity is a useful and non-invasive method to monitor bird exposure to anticholinesterase compounds; nonetheless several studies had shown that the ChE form(s present in avian plasma may vary greatly among species. In order to support further biomonitoring studies and provide reference data for wildlife risk-assessment, plasma cholinesterase of the northern gannet (Morus bassanus, the white stork (Ciconia ciconia and the grey heron (Ardea cinerea were characterized using three substrates (acetylthiocholine iodide, propionylthiocholine iodide, and S-butyrylthiocholine iodide and three ChE inhibitors (eserine sulphate, BW284C51, and iso-OMPA. Additionally, the range of ChE activity that may be considered as basal levels for non-exposed individuals was determined. The results suggest that in the plasma of the three species studied the main cholinesterase form present is butyrylcholinesterase (BChE. Plasma BChE activity in non-exposed individuals was 0.48±0.11 SD U/ml, 0.39±0.12 SD U/ml, 0.15±0.04 SD U/ml in the northern gannet, white stork and grey heron, respectively. These results are crucial for the further use of plasma BChE activity in these bird species as a contamination bioindicator of anti-cholinesterase agents in both wetland and marine environments. Our findings also underscore the importance of plasma ChE characterization before its use as a biomarker in biomonitoring studies with birds.
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.
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.
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.
Influence of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference in rats.

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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
Cholinesterase inhibition and acetylcholine accumulation following intracerebral administration of paraoxon in rats

International Nuclear Information System (INIS)

Ray, A.; Liu, J.; Karanth, S.; Gao, Y.; Brimijoin, S.; Pope, C.

2009-01-01

We evaluated the inhibition of striatal cholinesterase activity following intracerebral administration of paraoxon assaying activity either in tissue homogenates ex vivo or by substrate hydrolysis in situ. Artificial cerebrospinal fluid (aCSF) or paraoxon in aCSF was infused unilaterally (0.5 μl/min for 2 h) and ipsilateral and contralateral striata were harvested for ChE assay ex vivo. High paraoxon concentrations were needed to inhibit ipsilateral striatal cholinesterase activity (no inhibition at < 0.1 mM; 27% at 0.1 mM; 79% at 1 mM paraoxon). With 3 mM paraoxon infusion, substantial ChE inhibition was also noted in contralateral striatum. ChE histochemistry generally confirmed these concentration- and side-dependent effects. Microdialysates collected for up to 4 h after paraoxon infusion inhibited ChE activity when added to striatal homogenate, suggesting prolonged efflux of paraoxon. Since paraoxon efflux could complicate acetylcholine analysis, we evaluated the effects of paraoxon (0, 0.03, 0.1, 1, 10 or 100 μM, 1.5 μl/min for 45 min) administered by reverse dialysis through a microdialysis probe. ChE activity was then monitored in situ by perfusing the colorimetric substrate acetylthiocholine through the same probe and measuring product (thiocholine) in dialysates. Concentration-dependent inhibition was noted but reached a plateau of about 70% at 1 μM and higher concentrations. Striatal acetylcholine was below the detection limit at all times with 0.1 μM paraoxon but was transiently elevated (0.5-1.5 h) with 10 μM paraoxon. In vivo paraoxon (0.4 mg/kg, sc) in adult rats elicited about 90% striatal ChE inhibition measured ex vivo, but only about 10% inhibition measured in situ. Histochemical analyses revealed intense AChE and glial fibrillary acidic protein staining near the cannula track, suggesting proliferation of inflammatory cells/glia. The findings suggest that ex vivo and in situ cholinesterase assays can provide very different views into enzyme
Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of cholinesterase inhibitors.

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

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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

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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
The modified amino sugarN-Butyryl Glucosaminefed toovariectomized ratspreservesbone mineralthroughincreased early mineralization,but does not affect body composition

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Tassos Anastassiades

2017-10-01

Full Text Available Background: The toxicities of pharmaceuticals for chronic arthritis and osteoporosis should be of concern to consumers. This partially accounts for the popularity of consumption of the amino sugar glucosamine, in-spite of controversy about its efficacy. We chemically synthesized N-butyryl glucosamine (GlcNBu, which we discovered protected bone and cartilage in an inflammatory arthritis rat model when used as a feed supplement. GlcNBu can also be potentially synthesized biochemically, since we recently demonstrated that human acetyl-CoA: glucosamine-6-phosphate N-acetyltransferase 1 has a relaxed donor specificity and transfers acyl groups of up to four carbons in length, i.e. the butyryl moiety. Oral GlcNBu had no detectable toxicity and also protected against bone loss in ovariectomized (OVX rats as a model for osteoporosis. However, we demonstrated this only for bones excised at 6 months. Thus, the current study aims to determine when bone mineralization is maximized during daily GlcNBu supplementation, in both OVΧ and Sham-OVX rats, in addition to the relationship of bone mineralization to body composition. Methods: Female Sprague-Dawley rats were randomized into 4 groups, containing 8 rats each. The groups consisted of OVX or Sham-OVX rats whose diets were supplemented with either 200 mg/kg/day of GlcNBu or an equimolar amount of glucose. We performed sequential bone density and body composition measurements, by dual-energy X-ray absorptiometry in the live, anesthetised rats, over a 6-month experimental period, starting at the age of 8 weeks. Results were analyzed by descriptive statistics and 2-way ANOVA. Results: The major increases in the mineral content and density of the spine and the femur in GlcNBu-supplemented rats occurred early, from the baseline to week 8. Ovariectomy resulted in a number of significant differences in body composition, while feeding GlcNBu had no significant effects on body composition. The significant effects of

Synthesis of dibenzodioxazocines and their effects on cholinesterases and muscarinic cholinergic receptors.

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Gaál, J; Batke, J; Borsodi, A; Rózsa, L; Somogyi, G

1989-01-01

A new family of tricyclic compounds, the dibenzodioxazocines were synthesized. These compounds were the following: 2-chloro-12-(2-piperidino-ethyl)-dibenzo d,g 1,3,6 dioxazocine hydrochloride: EGYT-2347, 2-chloro-12-(3-dimethylamino-2-methyl-propyl)-dibenzo [d,g] [1,3,6]-dibenzodioxazocine hydrochloride: EGYT-2509, 2-chloro-12-(3-dimethylamino-propyl)-dibenzo [d,g] [1,3,6] dioxazocine-maleate: EGYT-2474 and 2-chloro-12-2-(4-methyl-piperazino)-ethyl-dibenzo [d,g] [1,3,6]-dioxazocine-dihydrochloride: EGYT-2541. These compounds are inhibitors of both butyryl- and acetylcholinesterase to and they exhibited relatively good anticholinergic properties in receptor binding experiments. The most selective inhibitor of butyrylcholinesterase is the compound EGYT-2347 (Ki = 1.5 x 10(-7) M) which strongly binds to rat brain muscarinic cholinergic receptor (KD = 4.1 x 10(-8) M).
Cholinesterase Enzymes Inhibitors from the Leaves of Rauvolfia Reflexa and Their Molecular Docking Study

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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.

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

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

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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.
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.
[Insect cholinesterases and irreversible inhibitors. Statistical treatment of the data].

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Moralev, S N

2010-01-01

The data on sensitivity of cholinesterases (ChE) of different insects to reversible inhibitors, as well as the data on physico-chemical parameters of amino acids constituting their active centers, were treated by factor analysis and juxtaposed. It is shown that both these characteristics are related to taxonomical belonging of insects. It is revealed the "material substrate" of the factors determining inhibitor action specificity, which are specific sites in ChE active center.
[Correlation and interconversion between erythrocyte cholinesterase values obtained by the Michel and the EQM techniques].

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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

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

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

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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.
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.

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

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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.
A longitudinal study of risk factors for community-based home help services in Alzheimer’s disease: the influence of cholinesterase inhibitor therapy

Directory of Open Access Journals (Sweden)

Wattmo C

2013-03-01

Full Text Available Carina Wattmo, Elisabeth Paulsson, Lennart Minthon, Elisabet LondosClinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Malmö, SwedenBackground: To investigate the long-term effects of cholinesterase inhibitor (ChEI therapy and the influence of sociodemographic and clinical factors on the use of community-based home help services (HHS by patients with Alzheimer’s disease (AD.Methods: This 3-year, prospective, multicenter study included 880 AD patients treated with donepezil, rivastigmine, or galantamine in a routine clinical setting. At baseline and every 6 months, the patients were assessed with several rating scales, including the Mini-Mental State Examination, Instrumental Activities of Daily Living (IADL, and Physical Self-Maintenance Scale. Doses of ChEI and amounts of HHS per week were recorded. Cox regression models were used to predict the time to HHS, and multiple linear regression was used to predict the volume of HHS used.Results: During the study, 332 patients (38% used HHS. Factors that both postponed HHS use and predicted lower amounts of HHS were higher doses of ChEIs, better IADL ability, and living with family. Men, younger individuals, and those with a slower IADL decline showed a longer time to HHS, whereas female sex, a lower cognitive status, or more medications at baseline predicted fewer hours of HHS.Conclusions: Higher doses of ChEI might reduce the use of HHS, possibly reducing the costs of community-based care. Female spouses provide more informal care than do male spouses, so the likelihood of using HHS is greater among women with AD. The "silent group" of more cognitively impaired and frail elderly AD patients receives less HHS, which might precipitate institutionalization.Keywords: cognition, activities of daily living, treatment effect, gender, predictors
The intracellular domain of the Drosophila cholinesterase-like neural adhesion protein, gliotactin, is natively unfolded

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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
Application of enzyme multibiosensor for toxicity analysis of real water samples of different origin

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Soldatkin A. P.

2009-06-01

Full Text Available Aim. The analysis of toxicity of different water samples with the multibiosensor developed earlier. Methods. The potentiometric multibiosensor with several immobilized enzymes as bioselective elements and the matrix of pH-sensitive field effect transistors as transducers of the biochemical signal into the electric one was applied for the analysis. Results. The bioselective elements of the multibiosensor were developed using acetylcholinesterase, butyryl- cholinesterase, urease, glucose oxidase, and three-enzyme system (invertase, mutarotase, glucose oxidase. The measurement of toxic compounds in water samples of different origin was performed using the constructed sensor. The results obtained were compared with those obtained by the conventional methods of toxic agent’s analysis (atomic absorption spectrometry, thin-film chroma- tography, and atomic absorbic analyser of mercury. Conclusion. A strong conformity between the results obtained with the multibiosensor and traditional methods has been shown.
Arylesterase Phenotype-Specific Positive Association Between Arylesterase Activity and Cholinesterase Specific Activity in Human Serum

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Yutaka Aoki

2014-01-01

Full Text Available Context: Cholinesterase (ChE specific activity is the ratio of ChE activity to ChE mass and, as a biomarker of exposure to cholinesterase inhibitors, has a potential advantage over simple ChE activity. Objective: To examine the association of several potential correlates (serum arylesterase/paraoxonase activity, serum albumin, sex, age, month of blood collection, and smoking with plasma ChE specific activity. Methods: We analyzed data from 195 cancer-free controls from a nested case-control study, accounting for potential confounding. Results: Arylesterase activity had an independent, statistically significant positive association with ChE specific activity, and its magnitude was the greatest for the arylesterase phenotype corresponding to the QQ PON1192 genotype followed by phenotypes corresponding to QR and RR genotypes. Serum albumin was positively associated with ChE specific activity. Conclusions: Plasma arylesterase activity was positively associated with plasma ChE specific activity. This observation is consistent with protection conferred by a metabolic phenotype resulting in reduced internal dose.
O-Hydroxyl- or o-amino benzylamine-tacrine hybrids: multifunctional biometals chelators, antioxidants, and inhibitors of cholinesterase activity and amyloid-β aggregation.

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

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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.

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

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

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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.
Different Cholinesterase Inhibitor Effects on CSF Cholinesterases in Alzheimer Patients

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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
Estimation of plasma tacrine concentrations using an in vitro cholinesterase inhibition assay

International Nuclear Information System (INIS)

Moriearty, P.L.; Kenny, W.; Kumar, V.

1989-01-01

THA (9-amino, 1,2,3,4-tetrahydroacridine; tacrine) is currently under study as a cholinesterase (ChE) inhibitor in Alzheimer disease. In this study, a sensitive radiometric assay for THA inhibition of human plasma ChE, suitable for detection of effects of orally administered drug, is described. The assay is sensitive in a range of 4-50 ng/ml plasma. Reversibility of the inhibition permits distinguishing of drug effects on ChE from changes in amount of enzyme synthesized during treatment
Changes in glutathione system and lipid peroxidation in rat blood during the first hour after chlorpyrifos exposure

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V. P. Rosalovsky

2015-10-01

Full Text Available Chlorpyrifos (CPF is a highly toxic organophosphate compound, widely used as an active substance of many insecticides. Along with the anticholinesterase action, CPF may affect other biochemical mechanisms, particularly through disrupting pro- and antioxidant balance and inducing free-radical oxidative stress. Origins and occurrence of these phenomena are still not fully understood. The aim of our work was to investigate the effects of chlorpyrifos on key parameters of glutathione system and on lipid peroxidation in rat blood in the time dynamics during one hour after exposure. We found that a single exposure to 50 mg/kg chlorpyrifos caused a linear decrease in butyryl cholinesterase activity, increased activity of glutathione peroxidase and glutathione reductase, alterations in the levels of glutathione, TBA-active products and lipid hydroperoxides during 1 hour after poisoning. The most significant changes in studied parameters were detected at the 15-30th minutes after chlorpyrifos exposure.
Crystal structure, phytochemical study and enzyme inhibition activity of Ajaconine and Delectinine

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Ahmad, Shujaat; Ahmad, Hanif; Khan, Hidayat Ullah; Shahzad, Adnan; Khan, Ezzat; Ali Shah, Syed Adnan; Ali, Mumtaz; Wadud, Abdul; Ghufran, Mehreen; Naz, Humera; Ahmad, Manzoor

2016-11-01

The Crystal structure, comparative DFT study and phytochemical investigation of atisine type C-20 diterpenoid alkaloid ajaconine (1) and lycoctonine type C-19 diterpenoid alkaloid delectinine (2) is reported here. These compounds were isolated from Delphinium chitralense. Both the natural products 1 and 2 crystallize in orthorhombic crystal system with identical space group of P212121. The geometric parameters of both compounds were calculated with the help of DFT using B3LYP/6-31+G (p) basis set and HOMO-LUMO energies, optimized band gaps, global hardness, ionization potential, electron affinity and global electrophilicity are calculated. The compounds 1 and 2 were screened for acetyl cholinesterase and butyryl cholinesterase inhibition activities in a dose dependent manner followed by molecular docking to explore the possible inhibitory mechanism of ajaconine (1) and delectinine (2). The IC50 values of tested compounds against AChE were observed as 12.61 μM (compound 1) and 5.04 μM (compound 2). The same experiments were performed for inhibition of BChE and IC50 was observed to be 10.18 μM (1) and 9.21 μM (2). Promising inhibition activity was shown by both the compounds against AChE and BChE in comparison with standard drugs available in the market such as allanzanthane and galanthamine. The inhibition efficiency of both the natural products was determined in a dose dependent manner.
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.
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.
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.

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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.
Inhibition of cholinesterase by essential oil from food plant.

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

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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.

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

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

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

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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.

Monitoring of plasma butyrylcholinesterase activity and hematological parameters in pesticide sprayers.

Science.gov (United States)

Rastogi, S K; Singh, Vipul K; Kesavachandran, C; Jyoti; Siddiqui, M K J; Mathur, N; Bharti, R S

2008-04-01

To evaluate the health impact of spraying organophosphorus insecticides (OPs), 34 male sprayers in the mango belt of Malihabad, a small town located 27 km from Lucknow in North India was selected. Plasma butyryl cholinesterase (PBChE) and complete blood count were assessed among sprayers after spraying pesticides and the findings obtained were compared with those determined in a reference group (n = 18). The most common symptoms observed were burning sensation in the eyes (8.82%), itching/skin irritation (23.52%) and chest symptoms (32.35%) in the exposed workers. Plasma butyrylcholinesterase (PBChE) was significantly decreased in workers. The results indicated significant decrease in the mean value of hemoglobin, hematocrit and platelets count; however, significantly higher count of leukocytes was also observed in the exposed group (sprayers) compared to that observed in the control group (P < 0.05). Monitoring of PBChE in pesticide sprayers could be useful to predict and prevent health hazards of OPs.
Botanical Sources for Alzheimer's: A Review on Reports From Traditional Persian Medicine.

Science.gov (United States)

Hosseinkhani, Ayda; Sahragard, Ali; Namdari, Aida; Zarshenas, Mohammad M

2017-11-01

Herbal medicines for the treatment of Alzheimer's disease (AD) have attracted considerable attention nowadays. Alzheimer's disease is described in traditional Persian medicine (TPM) by the term Nesyān. In this study, 5 main medicinal medieval Persian manuscripts were reviewed to filter plants reported for the treatment of Nesyān. Databases were searched for related possible mechanisms of action of these medicinal plants. Each herb was searched for along with these keywords: "acetyl and butyryl cholinesterase inhibition," "antioxidant," "anti-inflammatory," and "anti-amyloidogenic." In Total, 44 herbs were used for the treatment of Nesyān; 40 of those were authenticated. Also, 30 plants had at least one of the mechanisms of action that were searched for or related pharmacological functions known for the treatment of AD. In this work, we introduce promising candidates in TPM that could undergo further investigation for identification of their active compounds and clinical validation in the treatment of AD.
Protective effects of the dietary supplementation of turmeric (Curcuma longa L.) on sodium arsenite-induced biochemical perturbation in mice.

Science.gov (United States)

Karim, Md Rezaul; Haque, Abedul; Islam, Khairul; Ali, Nurshad; Salam, Kazi Abdus; Saud, Zahangir Alam; Hossain, Ekhtear; Fajol, Abul; Akhand, Anwarul Azim; Himeno, Seiichiro; Hossain, Khaled

2010-12-01

The present study was undertaken to evaluate the protective effect of turmeric powder on arsenic toxicity through mice model. Swiss albino male mice were divided into four groups. The first group was used as control, while groups 2, 3, and 4 were treated with turmeric powder (T, 50 mg/kg body weight/day), sodium arsenite (Sa, 10 mg/kg body weight/day) and turmeric plus Sa (T+Sa), respectively. Results showed that oral administration of Sa reduced the weight gain of the mice compared to the control group and food supplementation of turmeric prevented the reduction of weight gain. Turmeric abrogated the Sa-induced elevation of serum urea, glucose, triglyceride (TG) level and alanine aminotransferase (ALT) activity except the activity of alkaline phosphatase (ALP). Turmeric also prevented the Sa-induced perturbation of serum butyryl cholinesterase activity (BChE). Therefore, ameliorating effect of turmeric on Sa-treated mice suggested the future application of turmeric to reduce or to prevent arsenic toxicity in human.
[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.
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
[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.
Modulation of fusiform cortex activity by cholinesterase inhibition predicts effects on subsequent memory.

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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.
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
Early appearance and possible roles of non-neuromuscular cholinesterases.

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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.
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
Pesticide Application and Khat Chewing as Predictors of the Neurological Health Outcomes among Pesticide Applicators in a Vector Control Unit, Saudi Arabia

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Ahmed A Ismail

2018-01-01

Full Text Available Background: Pesticide applicators are at risk of developing neurological symptoms and neurobehavioral deficits. This risk may increase if the applicator chews stimulant plants like khat. Objective: To examine the sociodemographic and exposure determinants of neurological symptoms presentation, neurobehavioral performance, and cholinesterase activity among pesticide applicators in a vector control unit, Saudi Arabia. Methods: In a cross-sectional study, 30 pesticide applicators and 32 non-applicators from a vector control unit in Jazan region, Saudi Arabia, were studied. The study participants completed an exposure and medical questionnaire, and a neurobehavioral test battery. Their blood samples were also tested for the measurement of butyryl cholinesterase (BChE. Results: The mean blood BChE level was no significantly different between the applicators and non-applicators. Working in pesticide application and chewing khat were significant predictors of the neurological symptoms presentation and neurobehavioral deficits among the study participants. Each factor was associated with about 40% of the symptoms included in the questionnaire. Exposure to pyrethroids was significantly associated with a decrement in symbol digit test latency, tapping (TAP non-preferred hand, and TAP alternating hands measures, representing the executive and motor speed/coordination functions. Khat chewing was associated with TAP preferred and non-preferred hands and serial digit learning measures, representing the memory and motor speed/coordination functions. Conclusions: It seems that being exposed to pyrethroids and chewing khat are associated with neurological and neurobehavioral drawbacks among pesticide applicators.
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.

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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.
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.
Cholinesterase inhibitor use is associated with increased plasma levels of anti-Aβ 1-42 antibodies in Alzheimer's disease patients.

Science.gov (United States)

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.
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...
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.
Acetylcholine turnover in mouse brain: influence of cholinesterase inhibitors

International Nuclear Information System (INIS)

Karlen, B.; Holmstedt, B.; Lundgren, G.; Lundin, J.

1986-01-01

The authors determine whether the irreversible cholinesterase inhibitors soman, sarin or FX, which are thought to increase brain ACh concentration by a mechanism different to that of the muscarinic receptor agonist oxotremorine, also would decrease the turnover rate of brain ACh. Male albino mice were used in the study. N-(2-hydroxyethyl-N,N,N-tri-( 2 H 3 )methylammonium iodide and N-(2-acetoxyethyl)-N,N,N-tri-( 2 H 3 )methylammonium iodide were used as internal standards. N-(2-acetoxyethyl)-N,N,N,-tri-( 2 H 3 ), ( 1 H)methylammonium iodide was used for calibration purposes. The concentrations of Ch, ACh and their deuterated variants found in whole brain and striatum after pretreatment with saline, soman, sarin and FX are shown. In whole brain the endogeneous concentration of Ach was not affected by sarin and only to a slight but significant extent by Fs, while soman increased the level to about 30 nmol/g. All three substances increased the ch level in comparison to controls
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.
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.
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.
Alzheimer Disease: Pharmacologic and Nonpharmacologic Therapies for Cognitive and Functional Symptoms.

Science.gov (United States)

Epperly, Ted; Dunay, Megan A; Boice, Jack L

2017-06-15

Alzheimer disease comprises a syndrome of progressive cognitive and functional decline. Treatments should target cognitive and functional symptoms. Cholinesterase inhibitors, memantine, and a combination of a cholinesterase inhibitor and memantine have produced statistically significant but clinically small delays in various domains of cognitive and functional decline in select patients with Alzheimer disease. Vitamin E has been shown to delay functional decline in patients with mild to moderate Alzheimer disease, especially when taken in combination with a cholinesterase inhibitor. Structured programs of physical exercise improve physical function and reduce rates of neuropsychiatric symptoms in patients with mild to severe Alzheimer disease. Cognitive stimulation programs show benefit in maintenance of cognitive function and improved self-reported quality of life in patients with mild to moderate Alzheimer disease.
Diethyl 2-(Phenylcarbamoylphenyl Phosphorothioates: Synthesis, Antimycobacterial Activity and Cholinesterase Inhibition

Directory of Open Access Journals (Sweden)

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.
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.

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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

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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.
DEPRESSION OF THE PHOTIC AFTER DISCHARGE OF FLASH EVOKED POTENTIALS BY PHYSOSTIGMINE, CARBARYL AND PROPOXUR AND THE RELATIONSHIP TO INHIBITION OF BRAIN CHOLINESTERASE

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The effects of N-methyl carbamate pesticides on the photic after discharge (PhAD) of flash evoked potentials (FEPs) and the relationship between inhibition of brain cholinesterase (ChE) activity and the PhAD were evaluated. FEPs were recorded in Long Evans rats treated with physo...
Development of organophosphate hydrolase activity in a bacterial homolog of human cholinesterase

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

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

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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.

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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.

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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.
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

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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

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

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

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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.
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.
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.
[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).
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.
Light therapy modulates serotonin levels and blood flow in women with headache. A preliminary study.

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Tomaz de Magalhães, Miriam; Núñez, Silvia Cristina; Kato, Ilka Tiemy; Ribeiro, Martha Simões

2016-01-01

In this study, we looked at the possible effects of low-level laser therapy (LLLT) on blood flow velocity, and serotonin (5-HT) and cholinesterase levels in patients with chronic headache associated with temporomandibular disorders (TMD). LLLT has been clinically applied over the past years with positive results in analgesia and without the report of any side effects. The understanding of biological mechanisms of action may improve clinical results and facilitate its indication. Ten patients presenting headache associated with TMD completed the study. An 830-nm infrared diode laser with power of 100 mW, exposure time of 34 s, and energy of 3.4 J was applied on the tender points of masseter and temporal muscle. Blood flow velocity was determined via ultrasound Doppler velocimetry before and after laser irradiation. The whole blood 5-HT and cholinesterase levels were evaluated three days before, immediately, and three days after laser irradiation. Pain score after treatment decreased to a score of 5.8 corresponding to 64% of pain reduction (P 0.05). Our findings indicated that LLLT regulates blood flow in the temporal artery after irradiation and might control 5-HT levels in patients suffering with tension-type headache associated to TMD contributing to pain relief. © 2016 by the Society for Experimental Biology and Medicine.
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
Review of UV spectroscopic, chromatographic, and electrophoretic methods for the cholinesterase reactivating antidote pralidoxime (2-PAM).

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

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

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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 Â© 2010 Elsevier Masson SAS. All rights reserved.
Divergent effects of postmortem ambient temperature on organophosphorus- and carbamate-inhibited brain cholinesterase activity in birds

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Hill, E.F.

1989-01-01

Time- and temperature-dependent postmortem changes in inhibited brain cholinesterase (ChE) activity may confound diagnosis of field poisoning of wildlife by anticholinesterase pesticide. Carbamate-inhibited ChE activity may return to normal within 1 to 2 days of exposure of intact carcass to moderate ambient temperature (18-32C). Organophosphorus-inhibited ChE activity becomes more depressed over the same time. Uninhibited ChE activity was resilient to above freezing temperature to 32C for 1 day and 25C for 3 days. Carbamate- and organophosphorus-inhibited ChE can be separated by incubation of homogenate for 1 hour at physiological temperatures; carbamylated ChE can be readily reactivated while phosphorylated ChE cannot.
Accumulation of phenolic compounds in in vitro cultures and wild plants of Lavandula viridis L'Hér and their antioxidant and anti-cholinesterase potential.

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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.
State-wide hospital clinical laboratory plan for measuring cholinesterase activity for individuals suspected of exposure to nerve agent chemical weapons.

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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.
Therapy against organophosphate poisoning: The importance of anticholinergic drugs with antiglutamatergic properties

International Nuclear Information System (INIS)

Weissman, Ben Avi; Raveh, Lily

2008-01-01

Potent cholinesterase inhibitors (e.g., soman, sarin), induce a wide range of deleterious effects including convulsions, behavioral impairments and ultimately, death. Due to the likelihood of various scenarios of military or terrorist attacks by these and other chemical weapons, research has to be aimed at finding optimal therapies. Early accumulation of acetylcholine in synaptic clefts was suggested to trigger an array of toxic events including an excessive release of glutamate, culminating in the activation of its receptors. Stimulation of the N-Methyl-D-Aspartate (NMDA) subtype of these receptors was associated with the neuronal injury that initiates organophosphate-induced brain damage. The notion of a stepwise mechanism yielded treatments based on a combination of an immediate administration of enzyme reactivators and anticholinergic drugs. This strategy dramatically increased survival rates but did not abolish convulsions and failed to prevent the ensuing cognitive dysfunction. Efforts to improve this paradigm by adding anticonvulsants or antiglutamatergic drugs with anti-epileptic characteristics produced dubious results. Under these conditions, benactyzine and caramiphen, agents with anticholinergic and antiglutamatergic properties, provided improved protection when introduced as adjunct agents to oximes, reversible cholinesterase inhibitors and/or specific antimuscarinic drugs such as atropine. In contrast, the specific antimuscarinic drug scopolamine failed to block soman-induced changes in glutamatergic and behavioral parameters even when given prophylactically. These findings along with a large number of additional reports led towards the conclusion that the therapeutic advantage of drugs such as benactyzine and caramiphen could derive from their ability to modulate central cholinergic and glutamate neurotransmission
PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos

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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

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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.
[The activity of blood cholinesterase in rats exposed to dimehypo].

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

2002-12-01

To determine whether and to what degree the activity of cholinesterase(ChE) is inhibited by dimehypo at different doses of dimehypo [scientific name: 2-dimethylamine-1,3-bi(sodium hyposulfit)]. Rats were dosed with dimehypo or methamidophos orally, and were randomly divided into four subgroups according to the pesticide doses, which were 1/16, 1/8, 1/4 and 1/2 of LD50 respectively(the LD50 of dimethypo and methamidophos is 342 mg/kg and 20 mg/kg respectively). The activity of ChE in blood was determined before and 30 min, 1, 2, 4 and 24 h after exposure. The modified Ellman Method was employed to measure the activity of ChE. 1/16 LD50 dose of dimehypo did not affect the activity of ChE. When the dose increased, the activity of ChE decreased accordingly. 1/2 LD50 dose of dimehypo inhibited the activity of ChE by 35.9% compared with that of control group(P dimehypo at various doses was significantly lower than that in the rats dosed with corresponding doses of methamidophos(P dimehypo may inhibit the activity of ChE. However, as compared with methamidophos, dimehypo is a weaker inhibitor of ChE.
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.
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.
[Comparative analysis of sensitivity of proteases (chymotrypsin and trypsin) and cholinesterases of different origin to some organophosphorus inhibitors].

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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.
A comprehensive evaluation of the efficacy of leading oxime therapies in guinea pigs exposed to organophosphorus chemical warfare agents or pesticides

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Wilhelm, Christina M., E-mail: wilhelmc@battelle.org [Battelle, 505 King Avenue, JM-7, Columbus, OH 43201-2693 (United States); Snider, Thomas H., E-mail: snidert@battelle.org [Battelle, 505 King Avenue, JM-7, Columbus, OH 43201-2693 (United States); Babin, Michael C., E-mail: babinm@battelle.org [Battelle, 505 King Avenue, JM-7, Columbus, OH 43201-2693 (United States); Jett, David A., E-mail: jettd@ninds.nih.gov [National Institutes of Health/National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892 (United States); Platoff, Gennady E., E-mail: platoffg@niaid.nih.gov [National Institutes of Health/National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892 (United States); Yeung, David T., E-mail: dy70v@nih.gov [National Institutes of Health/National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892 (United States)

2014-12-15

The currently fielded pre-hospital therapeutic regimen for the treatment of organophosphorus (OP) poisoning in the United States (U.S.) is the administration of atropine in combination with an oxime antidote (2-PAM Cl) to reactivate inhibited acetylcholinesterase (AChE). Depending on clinical symptoms, an anticonvulsant, e.g., diazepam, may also be administered. Unfortunately, 2-PAM Cl does not offer sufficient protection across the range of OP threat agents, and there is some question as to whether it is the most effective oxime compound available. The objective of the present study is to identify an oxime antidote, under standardized and comparable conditions, that offers protection at the FDA approved human equivalent dose (HED) of 2-PAM Cl against tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX, and the pesticides paraoxon, chlorpyrifos oxon, and phorate oxon. Male Hartley guinea pigs were subcutaneously challenged with a lethal level of OP and treated at approximately 1 min post challenge with atropine followed by equimolar oxime therapy (2-PAM Cl, HI-6 DMS, obidoxime Cl{sub 2}, TMB-4, MMB4-DMS, HLö-7 DMS, MINA, and RS194B) or therapeutic-index (TI) level therapy (HI-6 DMS, MMB4-DMS, MINA, and RS194B). Clinical signs of toxicity were observed for 24 h post challenge and blood cholinesterase [AChE and butyrylcholinesterase (BChE)] activity was analyzed utilizing a modified Ellman's method. When the oxime is standardized against the HED of 2-PAM Cl for guinea pigs, the evidence from clinical observations, lethality, quality of life (QOL) scores, and cholinesterase reactivation rates across all OPs indicated that MMB4 DMS and HLö-7 DMS were the two most consistently efficacious oximes. - Highlights: • First comprehensive evaluation of leading AChE oxime reactivators • All oximes are compared against current U.S. therapy 2-PAM Cl. • Relative therapeutic oxime efficacies against OP CWNA and pesticides • Contribution to more effective
Black-bellied whistling duck (Dendrocygna autumnalis) brain cholinesterase characterization and diagnosis of anticholinesterase pesticide exposure in wild populations from Mexico.

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Osten, Jaime Rendón-von; Soares, Amadeu M V M; Guilhermino, Lucia

2005-02-01

Rice is the main crop in the subbasin of the fluvial lagoon system of Palizada River (FLSPR) in the state of Campeche, Mexico. The pesticides used to control pests of this crop mainly are carbofuran, chlorpyrifos, and glyphosate. Black-bellied whistling duck (Dendrocygna autumnalis) is an ecologically and economically important species in the area. This duck is consumed by local inhabitants throughout the year, despite its potential exposure to pesticides. Due to its feeding habits, abundance, and nutritional value, D. autumnalis is a good indicator of environmental contamination and a potential route of human exposure to organophosphate and carbamate pesticides. In this study, the brain cholinesterase (ChE) in the frontal cerebral cortex of autochthonous ducks was characterized. In addition, the potential of the three locally used pesticides and mixtures to inhibit ChE activity was investigated and the exposure of the wild duck population during intensive pesticide applications in rice fields was evaluated. We found that acetylcholinesterase (AChE) seems to be the predominant ChE form in the biological fraction analyzed. Carbofuran was the most potent ChE inhibitor of D. autumnalis brain ChE activity from the three pesticides analyzed. Cholinesterase inhibition after exposure to pesticide mixtures predominantly was due to carbofuran. A decrease (p 30%) was apparent in wild ducks compared to reference ducks, with recovery of ChE inhibition in wild ducks occurring months later when no pesticides were applied in the field. Dendrocygna autumnalis brain ChE is a suitable parameter for inclusion in biomonitoring programs for both environmental protection and human safety.
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.
Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors.

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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.
Coumarin derivatives bearing benzoheterocycle moiety: synthesis, cholinesterase inhibitory, and docking simulation study

Directory of Open Access Journals (Sweden)

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.
Radiolabelled soman binding to sera from Rats, Guinea Pigs and Monkeys.

Science.gov (United States)

Lenz, David E; Cerasoli, Douglas; Maxwell, Donald M

2018-02-01

Soman is a highly toxic organophosphorus chemical warfare compound that binds rapidly and irreversibility to a variety of serine active enzymes, i.e., butyryl- and acetyl-cholinesterases and carboxylesterase. The in vivo toxicity of soman has been reported to vary significantly in different animal species, such as rats and guinea pigs or non-human primates. This species variation makes it difficult to identify appropriate animal models for therapeutic drug development under the US Food and Drug Administration (FDA) Animal Rule. Since species variation in soman toxicity has been correlated with species variation in serum carboxylesterase, we undertook to determine if serum from guinea pigs, rats and non-human primates bound different levels of soman in vitro in the presence of equimolar concentrations of soman. Our results demonstrated that the amount of soman bound in the serum of rats was 4 uM, but essentially null in guinea pigs or non-human primates. The results strongly correlate with the presence or absence of carboxylesterase in the serum of animals and the difference in the toxic dose of soman in various species. Our results support prior suggestions that guinea pigs and non-human primates may be better animal models for the development of antidotes under the FDA Animal Rule. Published by Elsevier B.V.
Repetitive obidoxime treatment induced increase of red blood cell acetylcholinesterase activity even in a late phase of a severe methamidophos poisoning: A case report.

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Steinritz, Dirk; Eyer, Florian; Worek, Franz; Thiermann, Horst; John, Harald

2016-02-26

Accidental self-poisoning or deliberate use in suicidal intent of organophosphorus pesticides (OPP), which are widely used in agriculture, represent a health problem worldwide. Symptoms of poisoning are characterized by acute cholinergic crisis caused by inhibition of acetylcholinesterase. A 75-year-old male patient ingested 20ml of an OPP solution containing 10% methamidophos in suicidal intent. In the course of poisoning typical clinical symptoms of cholinergic crisis (miosis, bradycardia, hypotension, hypersalivation and impairment of neurologic status) were evident. Butyryl (plasma) cholinesterase (BChE) and red blood cell acetylcholinesterase (RBC-AChE) revealed decreased activities, thus specific treatment with the enzyme reactivator obidoxime was started. Inhibitory activity of the patient's plasma indicated significant amounts of persisting methamidophos in the circulation and was still found on day 4 after ingestion. Due to missing spontaneous breathing on day 6, obidoxime was administered again. Afterwards a significant increase of RBC-AChE activity was found. The patient was extubated on day 10 and a restitution ad integrum was achieved. In conclusion, obidoxime is a potent reactivator of OPP-inhibited AChE. A repetitive and prolonged administration of obidoxime should be considered in cases of severe methamidophos poisoning and should be tailored with an advanced analytical biomonitoring. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Blood cholinesterase activity levels of farmers in winter and hot season of Mae Taeng District, Chiang Mai Province, Thailand.

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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
Syntheses and characterization of novel oxoisoaporphine derivatives as dual inhibitors for cholinesterases and amyloid beta aggregation.

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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.

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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.
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.

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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...
The synthesis of carbon-14 labeled pravastatin

International Nuclear Information System (INIS)

Wallace, M.A.; Dean, D.C.; Ellsworth, R.L.; Melillo, D.G.; Marks, T.; White, R.F.

1993-01-01

An asymmetric route to [ 14 C]β-hydroxycompactin 1 bearing the (S)-2-methyl-[1- 14 C]butanoate side chain has been developed. Methylation of [N-[1- 14 C]butyryl]-4-(S)-phenylmethyl-2-oxazolidinone 4 afforded a 95:5 mixture of diastereomeric [N-(S,R)-2-methyl-[1- 14 C]butyryl]-4-(S)-phenylmethyl-2-oxazolidi nones 5,6 which were separated by preparative HPLC. Oxidative cleavage of 5 afforded optically pure (S)-2-methyl-[1- 14 C]butanoic acid. Acylation of alcohol 9 with optically pure (S)-2-methyl-[1- 14 C] butyryl chloride afforded ester 10. Removal of the silyl ether produced diastereomerically pure compactin 11. Hydroxylation was carried out by biotransformation with Mucor hiemelus to afford diastereomerically pure [[1- 14 C]butanoate]β-hydroxycompactin, [ 14 C]Pravastatin 1. (Author)
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.
1 effect and management of acute dichlorvos poisoning in wistar rats

African Journals Online (AJOL)

DR. AMINU

effect and antidotal therapy of dichlorvos was studied in laboratory animals. The LD50 in rats was ... sweating, involuntary muscle contractions and burning sensations or actual burns .... by inhibiting the cholinesterase enzyme in mammalian.
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.
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.

Cognitive stimulation therapy as a sustainable intervention for dementia in sub-Saharan Africa: feasibility and clinical efficacy using a stepped-wedge design.

Science.gov (United States)

Paddick, Stella-Maria; Mkenda, Sarah; Mbowe, Godfrey; Kisoli, Aloyce; Gray, William K; Dotchin, Catherine L; Ternent, Laura; Ogunniyi, Adesola; Kissima, John; Olakehinde, Olaide; Mushi, Declare; Walker, Richard W

2017-06-01

Cognitive stimulation therapy (CST) is a psychosocial group-based intervention for dementia shown to improve cognition and quality of life with a similar efficacy to cholinesterase inhibitors. Since CST can be delivered by non-specialist healthcare workers, it has potential for use in low-resource environments, such as sub-Saharan Africa (SSA). We aimed to assess the feasibility and clinical effectiveness of CST in rural Tanzania using a stepped-wedge design. Participants and their carers were recruited through a community dementia screening program. Inclusion criteria were DSM-IV diagnosis of dementia of mild/moderate severity following detailed assessment. No participant had a previous diagnosis of dementia and none were taking a cholinesterase inhibitor. Primary outcomes related to the feasibility of conducting CST in this setting. Key clinical outcomes were changes in quality of life and cognition. The assessing team was blind to treatment group membership. Thirty four participants with mild/moderate dementia were allocated to four CST groups. Attendance rates were high (85%) and we were able to complete all 14 sessions for each group within the seven week timeframe. Substantial improvements in cognition, anxiety, and behavioral symptoms were noted following CST, with smaller improvements in quality of life measures. The number needed to treat was two for a four-point cognitive (adapted Alzheimer's Disease Assessment Scale-Cognitive) improvement. This intervention has the potential to be low-cost, sustainable, and adaptable to other settings across SSA, particularly if it can be delivered by non-specialist health workers.
Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

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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 Structure-Activity Analysis of the Variation in Oxime Efficacy Against Nerve Agents

Science.gov (United States)

2008-01-01

cyclosarin. Analysis of in vivo oxime protection was conducted with oxime protective ratios (PR) from guinea pigs receiving oxime and atropine therapy ...in our study confirmed previous assessments that oxime protection varies drama - tically against different military nerve agents (Aas, 2003; Dawson... therapy ofacutepoisonings inducedbyanti-cholinesterase neuroparalytic substances. In:Monov, A., Dishovsky, C. (Eds.), Medical Aspects of Chemical and
Pharmacophore-based design and discovery of (-)-meptazinol carbamates as dual modulators of cholinesterase and amyloidogenesis.

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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.
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.
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.
Anticholinesterases: Medical applications of neurochemical principles

Energy Technology Data Exchange (ETDEWEB)

Millard, C.B.; Broomfield, C.A.

1995-12-31

Cholinesterases form a family of serine esterases that arise in animals from at least two distinct genes. Multiple forms of these enzymes can be precisely localized and regulated by alternative mRNA splicing and by co- or posttranslational modifications. The high catalytic efficiency of the cholinesterases is quelled by certain very selective reversible and irreversible inhibitors. Owing largely to the important role of acetylcholine hydrolysis in neurotransmission, cholinesterase and its inhibitors have been studied extensively in vivo. In parallel, there has emerged an equally impressive enzyme chemistry literature. Cholinesterase inhibitors are used widely as pesticides; in this regard the compounds are beneficial with concomitant health risks. Poisoning by such compounds can result in an acute but usually manageable medical crisis and may damage the ONS and the PNS, as well as cardiac and skeletal muscle tissue. Some inhibitors have been useful for the treatment of glaucoma and myasthenia gravis, and others are in clinical trials as therapy for Alzheimer`s dementia. Concurrently, the most potent inhibitors have been developed as highly toxic chemical warfare agents. We review treatments and sequelae of exposure to selected anticholinesterases, especially organophosphorus compounds and carbamates, as they relate to recent progress in enzyme chemistry.
The role of genetic background in susceptibility to chemical warfare nerve agents across rodent and non-human primate models.

Science.gov (United States)

Matson, Liana M; McCarren, Hilary S; Cadieux, C Linn; Cerasoli, Douglas M; McDonough, John H

2018-01-15

Genetics likely play a role in various responses to nerve agent exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses to environmental stimuli. Mouse strains or selected lines can be used to identify susceptibility based on background genetic features to nerve agent exposure. Additional genetic techniques can then be used to identify mechanisms underlying resistance and sensitivity, with the ultimate goal of developing more effective and targeted therapies. Here, we discuss the available literature on strain and selected line differences in cholinesterase activity levels and response to nerve agent-induced toxicity and seizures. We also discuss the available cholinesterase and toxicity literature across different non-human primate species. The available data suggest that robust genetic differences exist in cholinesterase activity, nerve agent-induced toxicity, and chemical-induced seizures. Available cholinesterase data suggest that acetylcholinesterase activity differs across strains, but are limited by the paucity of carboxylesterase data in strains and selected lines. Toxicity and seizures, two outcomes of nerve agent exposure, have not been fully evaluated for genetic differences, and thus further studies are required to understand baseline strain and selected line differences. Published by Elsevier B.V.
Partial protection from organophosphate-induced cholinesterase inhibition by metyrapone treatment

Directory of Open Access Journals (Sweden)

Radosław Świercz

2013-08-01

Full Text Available Background: Organophosphates are cholinesterase (ChE inhibitors with worldwide use as insecticides. Stress response, evidenced by a dramatic and relatively long-lasting (several hours rise in the plasma glucocorticoid concentration is an integral element of the organophosphate (OP poisoning symptomatology. In rodents, corticosterone (CORT is the main glucocorticoid. There are several reports suggesting a relationship between the stressor-induced rise in CORT concentraion (the CORT response and the activity of the cerebral and peripheral ChE. Thus, it seems reasonable to presume that, in OP intoxication, the rise in plasma CORT concentration may somehow affect the magnitude of the OP-induced ChE inhibition. Metyrapone (MET [2-methyl-1,2-di(pyridin-3-ylpropan-1-one] blocks CORT synthesis by inhibiting steoid 11β-hydroxylase, thereby preventing the CORT response. Chlorfenvinphos (CVP [2-chloro-1-(2,4-dichlorophenyl ethenyl diethyl phosphate] is an organophosphate insecticide still in use in some countries. Material and Methods: The purose of the present work was to compare the CVP-induced effects - the rise of the plasma CORT concentration and the reduction in ChE activity - in MET-treated and MET-untreated rats. Chlorfenvinphos was administered once at 0.0, 0.5, 1.0 and 3.0 mg/kg i.p. Metyrapone, at 100 mg/kg i.p., was administered five times, at 24-h intervals. The first MET dose was given two hours before CVP. Conclusion: The following was observed in the MET-treated rats: i no rise in plasma CORT concentration after the CVP administration, ii a reduced inhibition and a faster restitution of blood and brain ChE activities. The results suggest that MET treatment may confer significant protection against at least some effects of OP poisoning. The likely mechanism of the protective MET action has been discussed.
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.
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.
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.

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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...
Successful oxime therapy one hour after soman intoxication in the rat

NARCIS (Netherlands)

Wolthuis, O.L.; Kepner, L.A.

1978-01-01

The bisquarternary mono-oxime HI-6, and to a lesser extent HS-6, caused functional recovery of neuromuscular transmission in vivo and in vitro when given 60 min after soman, i.e. when the soman-cholinesterase (AChE) complex is said to be fully 'aged'. Atropinised rats, with the tracheas intubated,
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
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.
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.
Inhibition of Cholinesterases and Some Pro-Oxidant induced Oxidative Stress in Rats Brain by Two Tomato (Lycopersicon Esculentum) Varieties

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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.
Chemical Composition of Volatiles; Antimicrobial, Antioxidant and Cholinesterase Inhibitory Activity of Chaerophyllum aromaticum L. (Apiaceae) Essential Oils and Extracts.

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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.

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.
Dual functional cholinesterase and MAO inhibitors for the treatment of Alzheimer's disease: synthesis, pharmacological analysis and molecular modeling of homoisoflavonoid derivatives.

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

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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

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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
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.
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.
Cognitive intervention therapy as treatment for behaviour disorders in Alzheimer disease: evidence on efficacy and neurobiological correlations.

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García-Alberca, J M

2015-01-01

The prevalence of behavioural and psychological symptoms (BPS) is very high among patients with Alzheimer disease (AD); more than 90% of AD patients will present such symptoms during the course of the disease. These symptoms result in poorer quality of life for both patients and caregivers and increased healthcare costs. BPS are the main factors involved in increases to the caregiver burden, and they often precipitate the admission of patients to residential care centres. Current consensus holds that intervention models combining pharmacological and non-pharmacological treatments are the most effective for AD patients. Several studies have shown cholinesterase inhibitors and memantine combined with cognitive intervention therapy (CIT) to be effective for improving patients' cognitive function and functional capacity for undertaking daily life activities. However, the efficacy of CIT as a treatment for BPS has not yet been clearly established, which limits its use for this purpose in clinical practice. The objective of this review is to gather available evidence on the efficacy of cognitive intervention therapy (CIT) on BPS in patients with AD. The results of this review suggest that CIT may have a beneficial effect on BPS in patients with AD and should therefore be considered a treatment option for patients with AD and BPS. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.
Determination of esterase activity and characterization of cholinesterases in the reef fish Haemulon plumieri.

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Leticia, Alpuche-Gual; Gerardo, Gold-Bouchot

2008-11-01

White grunt (Haemulon plumieri) has been proposed by the Mesoamerican Barrier Reef System (MBRS) Synoptic Monitoring Program as a bioindicator species. It is in this sense that the present study has a main goal to evaluate this organism's suitability as an indicator species. Individuals were captured during three seasons at the port of Sisal, Yucatan, Mexico which is located in an area that is considered to be weakly impacted by human activities such as agriculture or industry. Both cholinesterase (ChE) and carboxylesterase (CbE) activities were measured in brain, muscle, liver and eye of sampled individuals. Results indicated that ChE and CbE activities were greatest in the brain (256.3 ± 43) and in the liver (191 ± 21), respectively. Furthermore, ChEs detected in brain, liver and muscle were characterized, and results suggested that the acetylcholinesterase (AChE) type was more abundant relative to pseudocholinesterase (BChE) which was rare. In addition, K(m) and V(max) and IC(50) values were calculated from the Michaelis-Menten equation. Finally, an additional experiment in vitro showed a significant decrease in both ChE and CbE activities when different tissues were exposed to model xenobiotics, such as benzo[a]pyrene and Chlorpyrifos. In conclusion, findings from this study confirm the potential suitability of H. plumieri as an organic pollution bioindicator species, and thus of practical use for environmental biomonitoring purposes.
The effect of stimulation therapy and donepezil on cognitive function in Alzheimer’s disease. A community based RCT with a two-by-two factorial design

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Andersen Fred

2012-07-01

Full Text Available Abstract Background Progressive neurodegeneration in Alzheimer’s disease (AD induces cognitive deterioration, and there is controversy regarding the optimal treatment strategy in early AD. Stimulation therapy, including physical exercise and cholinesterase inhibitors are both reported to postpone cognitive deterioration in separate studies. We aimed to study the effect of stimulation therapy and the additional effect of donepezil on cognitive function in early AD. Method Design: A two-by-two factorial trial comprising stimulation therapy for one year compared to standard care to which a randomized double-blinded placebo controlled trial with donepezil was added. Setting: Nine rural municipalities in Northern Norway. Participants: 187 participants 65 years and older with a recent diagnosis of mild or moderate AD were included in the study of which 146 completed a one-year follow-up. INTERVENTIONS: In five municipalities the participants received stimulation therapy whereas participants in four received standard care. All participants were randomised double-blindly to donepezil or placebo and tested with three different cognitive tests four times during the one-year study period. Main outcome: Changes in MMSE sum score. Secondary outcome: Changes in ADAS-Cog and Clock Drawing Test. Results MMSE scores remained unchanged amongst AD participants receiving stimulation therapy and those receiving standard care. The results were consistent for ADAS-Cog and Clock Drawing Test. No time trend differences were found during one-year follow-up between groups receiving stimulation therapy versus standard care or between donepezil versus placebo. Conclusion In rural AD patients non-pharmacological and pharmacological therapy did not improve outcome compared with standard care but all groups retained cognitive function during one year follow-up. Other studies are needed to confirm these results. Trial registration ClinicalTrials.gov (Identifier: NCT00443014
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.
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
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.

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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.
An Open-Label Exploratory Study with Memantine: Correlation between Proton Magnetic Resonance Spectroscopy and Cognition in Patients with Mild to Moderate Alzheimer’s Disease

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Marc L. Gordon

2012-08-01

Full Text Available Aim: To characterize progression of Alzheimer’s disease (AD using proton magnetic resonance spectroscopy (1H MRS. Methods: Eleven subjects with mild to moderate AD underwent neurocognitive testing and single-voxel 1H MRS from the precuneus and posterior cingulate region at baseline, after 24 weeks of monotherapy with a cholinesterase inhibitor, and after another 24 weeks of combination therapy with open-label memantine and a cholinesterase inhibitor. Baseline metabolites [N-acetylaspartate (NAA, myo-inositol (mI, choline (Cho, and creatine (Cr] and their ratios in AD subjects were compared with those of an age-matched control group of 28 cognitively normal subjects. Results: AD subjects had significantly higher mI/Cr and lower NAA, NAA/Cr, NAA/Cho, and NAA/mI. Baseline Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL scores significantly correlated with NAA/Cr, mI/Cr, and NAA/mI. There was an increase in mI and a decrease in NAA/mI, but no significant change in other metabolites or ratios, or neurocognitive measures, when memantine was added to a cholinesterase inhibitor. Conclusion: Metabolite ratios significantly differed between AD and control subjects. Baseline metabolite ratios correlated with function (ADCS-ADL. There was an increase in mI and a decrease in NAA/mI, but no changes in other metabolites, ratios, or cognitive measures, when memantine was added to a cholinesterase inhibitor.
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.
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

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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.
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.

Development of Optimized Guidelines for Therapeutic Strategies for Organophosphate Poisoning

Science.gov (United States)

2011-03-01

rhinorrhea, salivation, bronchorrhea, hypotension, nausea, vomiting, diarrhea, and bowel or urinary incontinence (Cannard, 2006). Nicotinic receptors...Several factors are responsible for the efficacy of oxime therapy, including the specific organophosphate, the route of exposure, and the route and...1987). That study looked at the inhibition of cholinesterase by soman in various organs and plasma of rats. To determine important factors related to
Comparative Effects of Oral Chlorpyrifos Exposure on Cholinesterase Activity and Muscarinic Receptor Binding in Neonatal and Adult Rat Heart

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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
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.
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.

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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.
Development of pretreatment compounds against nerve-gas agents. Annual report (Final), 16 May 88-30 Sep 90

Energy Technology Data Exchange (ETDEWEB)

Carroll, F.I.; Abraham, P.

1990-09-30

The U. S. Army Medical Research and Development Command is interested in research directed toward the development of countermeasures to chemical warfare (CW) agents such as the nerve gas poison soman. Soman and other nerve gas poisons are extremely potent cholinesterase inhibitors. This inhibition leads to a buildup of excess acetylcholine resulting in over-stimulation of both the peripheral and central nervous system and can lead to death. Standard therapy for organophosphate nerve agent poisoning is based on co-administration of an anticholinergic agent such as atropine to antagonize the effects of accumulated acetylcholine and a cholinesterase reactivator such as 2-PAM to dephosphorylate the inhibited enzyme. However, since many problems remain in the treatment of organophosphate nerve agent poisoning, there is considerable interest and need to develop new pretreatment and treatment drugs, particularly for soman poisoning.
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
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.
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.
Vibrational spectra of N-butyryl-homoserine lactone

DEFF Research Database (Denmark)

Bak, J.

A special class of organic compounds, N-acyl homoserine lactones (HSL), is synthesized in bacteria and takes part in the intercellular signaling designated quorum sensing. The outcome of the intercellular signaling is responsible for many of the interesting properties which characterize colony...... for a substantial part of morbidity and mortality in many medical specialties. Lactones are also interesting compounds from a spectroscopic point of view. The spectroscopic information about these compounds in the literature is very sparse. In this study we present the Mid-infrared spectra of homoserine lactones...
Antioxidant, anticancer and anticholinesterase activities of flower, fruit and seed extracts of Hypericum amblysepalum HOCHST.

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Keskin, Cumali

2015-01-01

Cancer is an unnatural type of tissue growth in which the cells exhibit unrestrained division, leading to a progressive increase in the number of dividing cells. It is now the second largest cause of death in the world. The present study concerned antioxidant, anticancer and anticholinesterase activities and protocatechuic, catechin, caffeic acid, syringic acid, p-coumaric acid and o-coumaric concentrations in methanol extracts of flowers, fruits and seeds of Hypericum amblysepalum. Antioxidant properties including free radical scavenging activity and reducing power, and amounts of total phenolic compounds were evaluated using different tests. Protocatechuic, catechin, caffeic acid, syringic acid, p-coumaric acid and o-coumaric concentrations in extracts were determined by HPLC. Cytotoxic effects were determined using the MTT test with human cervix cancer (HeLa) and rat kidney epithelium cell (NRK-52E) lines. Acetyl and butyrylcholinesterase inhibitory activities were measured by by Ellman method. Total phenolic content of H. amblysepalum seeds was found to be higher than in fruit and flower extracts. DPPH free radical scavenging activity of the obtained extracts gave satisfactory results versus butylated hydroxyanisole and butylated hydroxytoluene as controls. Reducing power activity was linearly proportional to the studied concentration range: 10-500 μg/ mL LC50 values for H. amblysepalum seeds were 11.7 and 2.86 respectively for HeLa and NRK-52E cell lines. Butyryl-cholinesterase inhibitory activity was 76.9±0.41 for seed extract and higher than with other extracts. The present results suggested that H. amblysepalum could be a potential candidate anti-cancer drug for the treatment of human cervical cancer, and good source of natural antioxidants.
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.
Comparison of neurological health outcomes between two adolescent cohorts exposed to pesticides in Egypt.

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Ahmed A Ismail

Full Text Available Pesticide-exposed adolescents may have a higher risk of neurotoxic effects because of their developing brains and bodies. However, only a limited number of studies have addressed this risk among adolescents. The aim of this study was to compare neurological outcomes from two cohorts of Egyptian adolescents working as pesticide applicators. In 2005 and 2009, two cohorts of male adolescents working as pesticide applicators for the cotton crop were recruited from Menoufia Governorate, Egypt. The same application schedule and pesticides were used at both times, including both organophosphorus, and pyrethroid compounds. Participants in both cohorts completed three neurobehavioral tests, health and exposure questionnaires, and medical and neurological screening examinations. In addition, blood samples were collected to measure butyryl cholinesterase (BChE activity. Pesticide applicators in both cohorts reported more neurological symptoms and signs than non-applicators, particularly among participants in the 2005 cohort (OR ranged from 1.18 to 15.3. Except for one test (Trail Making B, there were no significant differences between either applicators or non-applicators of both cohorts on the neurobehavioral outcome measures (p > 0.05. The 2005 cohort showed greater inhibition of serum BChE activity than the 2009 cohort (p < 0.05. In addition, participants with depressed BChE activity showed more symptoms and signs than others without BChE depression (p < 0.05. Our study is the first to examine the consistency of health outcomes associated with pesticide exposure across two cohorts tested at different times from the same geographical region in rural Egypt. This similar pattern of findings across the two cohorts provides strong evidence of the health impact of exposure of adolescents to pesticides.
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...
Does the cholinesterase inhibitor, donepezil, benefit both declarative and non-declarative processes in mild to moderate Alzheimer's disease?

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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.
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

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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.
Valores de referencia de la actividad de la colinesterasa eritrocitaria según las técnicas de Michel y EQM® en población laboral de Antioquia, Colombia Reference values for erythrocyte cholinesterase activity in the working population of Antioquia, Colombia, according to the Michel and EQM techniques

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Jaime Carmona-Fonseca

2003-11-01

Full Text Available OBJETIVO: Establecer valores de referencia de la actividad de la colinesterasa eritrocitaria (EC 3.1.1.7 para la población laboral activa de dos regiones del departamento de Antioquia, Colombia, situadas a diferentes alturas sobre el nivel del mar. MÉTODOS: Se diseñaron dos muestras representativas de la población laboral activa de 18 a 59 años de edad residente en el valle de Aburrá (1 540 m sobre el nivel del mar y en el cercano oriente antioqueño (2 150 m sobre el nivel del mar. Se excluyeron los trabajadores que empleaban sustancias inhibidoras de la colinesterasa en su trabajo o en el hogar, los que presentaban alguna enfermedad que alterara los niveles de colinesterasa y los que manifestaron no contar con buena salud. Se midió la actividad de la colinesterasa eritrocitaria con los métodos de Michel y EQM® en 827 personas, 415 de Aburrá y 412 del Oriente. Las proporciones se compararon mediante la prueba de ji al cuadrado, incluida la versión de Fisher. La prueba de la t de Student para muestras independientes se utilizó para la comparación de dos promedios. Para comparar simultáneamente tres o más promedios se empleó el análisis de la varianza, seguido del análisis de rangos múltiples de Newman-Keuls (ARM-NK. Cuando las variables no tenían distribución normal o cuando las varianzas no eran homogéneas se usó el análisis de la varianza no paramétrico de Kruskal y Wallis para comparar las medianas. Se emplearon los programas SPSS 9.0, SGPlus 7.1 y EpiInfo 6.04. En todas las pruebas estadísticas se aplicó un nivel de significación P OBJECTIVE: 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. METHODS: We took representative samples from populations of active working persons 18 to 59 years old from two regions in the department of
Endochondral Ossification Is Accelerated in Cholinesterase-Deficient Mice and in Avian Mesenchymal Micromass Cultures.

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Janine Spieker

Full Text Available Most components of the cholinergic system are detected in skeletogenic cell types in vitro, yet the function of this system in skeletogenesis remains unclear. Here, we analyzed endochondral ossification in mutant murine fetuses, in which genes of the rate-limiting cholinergic enzymes acetyl- (AChE, or butyrylcholinesterase (BChE, or both were deleted (called here A-B+, A+B-, A-B-, respectively. In all mutant embryos bone growth and cartilage remodeling into mineralizing bone were accelerated, as revealed by Alcian blue (A-blu and Alizarin red (A-red staining. In A+B- and A-B- onset of mineralization was observed before E13.5, about 2 days earlier than in wild type and A-B+ mice. In all mutants between E18.5 to birth A-blu staining disappeared from epiphyses prematurely. Instead, A-blu+ cells were dislocated into diaphyses, most pronounced so in A-B- mutants, indicating additive effects of both missing ChEs in A-B- mutant mice. The remodeling effects were supported by in situ hybridization (ISH experiments performed on cryosections from A-B- mice, in which Ihh, Runx2, MMP-13, ALP, Col-II and Col-X were considerably decreased, or had disappeared between E18.5 and P0. With a second approach, we applied an improved in vitro micromass model from chicken limb buds that allowed histological distinction between areas of cartilage, apoptosis and mineralization. When treated with the AChE inhibitor BW284c51, or with nicotine, there was decrease in cartilage and accelerated mineralization, suggesting that these effects were mediated through nicotinic receptors (α7-nAChR. We conclude that due to absence of either one or both cholinesterases in KO mice, or inhibition of AChE in chicken micromass cultures, there is increase in cholinergic signalling, which leads to increased chondroblast production and premature mineralization, at the expense of incomplete chondrogenic differentiation. This emphasizes the importance of cholinergic signalling in cartilage and
Potential anti-cholinesterase and β-site amyloid precursor protein cleaving enzyme 1 inhibitory activities of cornuside and gallotannins from Cornus officinalis fruits.

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

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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
Ethylmalonic aciduria is associated with an amino acid variant of short chain acyl-coenzyme A dehydrogenase

DEFF Research Database (Denmark)

Corydon, M J; Gregersen, N; Lehnert, W

1996-01-01

Ethylmalonic aciduria is a common biochemical finding in patients with inborn errors of short chain fatty acid beta-oxidation. The urinary excretion of ethylmalonic acid (EMA) may stem from decreased oxidation by short chain acyl-CoA dehydrogenase (SCAD) of butyryl-CoA, which is alternatively...

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

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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.
Resistance to inhibitors of cholinesterase (Ric-8A and Gαi contribute to cytokinesis abscission by controlling vacuolar protein-sorting (Vps34 activity.

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Cedric Boularan

Full Text Available Resistance to inhibitors of cholinesterase (Ric-8A is a guanine nucleotide exchange factor for Gαi, Gαq, and Gα12/13, which is implicated in cell signaling and as a molecular chaperone required for the initial association of nascent Gα subunits with cellular membranes. Ric-8A, Gαi subunits, and their regulators are localized at the midbody prior to abscission and linked to the final stages of cell division. Here, we identify a molecular mechanism by which Ric-8A affects cytokinesis and abscission by controlling Vps34 activity. We showed that Ric-8A protein expression is post-transcriptionally controlled during the cell cycle reaching its maximum levels at mitosis. A FRET biosensor created to measure conformational changes in Ric-8A by FLIM (Fluorescence Lifetime Imaging Microscopy revealed that Ric-8A was in a close-state during mitosis and particularly so at cytokinesis. Lowering Ric-8A expression delayed the abscission time of dividing cells, which correlated with increased intercellular bridge length and multinucleation. During cytokinesis, Ric-8A co-localized with Vps34 at the midbody along with Gαi and LGN, where these proteins functioned to regulate Vps34 phosphatidylinositol 3-kinase activity.
Traditional Chinese medicines and Alzheimer's disease.

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Wu, Tzong-Yuan; Chen, Chih-Ping; Chen, Chip-Ping; Jinn, Tzyy-Rong

2011-06-01

Traditional Chinese medicines have been widely investigated for the treatment of Alzheimer's disease (AD) because none of the current therapies-either the cholinesterase inhibitors or antagonist of N-methyl-d-aspartate receptors-has profound effects on halting the progression of AD. In recent years, scientists have isolated many active compounds from herbs, which can alleviate dementia and neurodegenerative syndrome with fewer side effects than conventional drugs and, thus, are regarded as promising drug candidates for AD therapy. In this review, we summarize the latest research progress on six herbs for AD therapy-Huperzia serrata, Amaryllidaceae family, Ginkgo biloba, Uncaria rhynchophylla, Polygala tenuifolia, and Salvia officinalis-and focus on the analysis of their active components and possible mechanisms of pharmacological actions on AD. Copyright © 2011. Published by Elsevier B.V.
Integrated Lateral Flow Test Strip with Electrochemical Sensor for Quantification of Phosphorylated Cholinesterase: Biomarker of Exposure to Organophosphorus Agents

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Du, Dan; Wang, Jun; Wang, Limin; Lu, Donglai; Lin, Yuehe

2012-02-08

An integrated lateral flow test strip with electrochemical sensor (LFTSES) device with rapid, selective and sensitive response for quantification of exposure to organophosphorus (OP) pesticides and nerve agents has been developed. The principle of this approach is based on parallel measurements of post-exposure and baseline acetylcholinesterase (AChE) enzyme activity, where reactivation of the phosphorylated AChE is exploited to enable measurement of total amount of AChE (including inhibited and active) which is used as a baseline for calculation of AChE inhibition. Quantitative measurement of phosphorylated adduct (OP-AChE) was realized by subtracting the active AChE from the total amount of AChE. The proposed LFTSES device integrates immunochromatographic test strip technology with electrochemical measurement using a disposable screen printed electrode which is located under the test zone. It shows linear response between AChE enzyme activity and enzyme concentration from 0.05 to 10 nM, with detection limit of 0.02 nM. Based on this reactivation approach, the LFTSES device has been successfully applied for in vitro red blood cells inhibition studies using chlorpyrifos oxon as a model OP agent. This approach not only eliminates the difficulty in screening of low-dose OP exposure because of individual variation of normal AChE values, but also avoids the problem in overlapping substrate specificity with cholinesterases and avoids potential interference from other electroactive species in biological samples. It is baseline free and thus provides a rapid, sensitive, selective and inexpensive tool for in-field and point-of-care assessment of exposures to OP pesticides and nerve agents.
Copper (II) and zinc (II) complexes with flavanone derivatives: Identification of potential cholinesterase inhibitors by on-flow assays.

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Sarria, André Lucio Franceschini; Vilela, Adriana Ferreira Lopes; Frugeri, Bárbara Mammana; Fernandes, João Batista; Carlos, Rose Maria; da Silva, Maria Fátima das Graças Fernandes; Cass, Quezia Bezerra; Cardoso, Carmen Lúcia

2016-11-01

Metal chelates strongly influence the nature and magnitude of pharmacological activities in flavonoids. In recent years, studies have shown that a promising class of flavanone-metal ion complexes can act as selective cholinesterase inhibitors (ChEIs), which has led our group to synthesize a new series of flavanone derivatives (hesperidin, hesperetin, naringin, and naringenin) complexed to either copper (II) or zinc (II) and to evaluate their potential use as selective ChEIs. Most of the synthesized complexes exhibited greater inhibitory activity against acetylcholinesterase (AChE) than against butyrylcholinesterase (BChE). Nine of these complexes constituted potent, reversible, and selective ChEIs with inhibitory potency (IC 50 ) and inhibitory constant (K i ) ranging from 0.02 to 4.5μM. Copper complexes with flavanone-bipyridine derivatives afforded the best inhibitory activity against AChE and BChE. The complex Cu(naringin)(2,2'-bipyridine) (11) gave IC 50 and K i values of 0.012±0.002 and 0.07±0.01μM for huAChE, respectively, which were lower than the inhibitory values obtained for standard galanthamine (IC 50 =206±30.0 and K i =126±18.0μM). Evaluation of the inhibitory activity of this complex against butyrylcholinesterase from human serum (huBChE) gave IC 50 and K i values of 8.0±1.4 and 2.0±0.1μM, respectively. A Liquid Chromatography-Immobilized Capillary Enzyme Reactor by UV detection (LC-ICER-UV) assay allowed us to determine the IC 50 and K i values and the type of mechanism for the best inhibitors. Copyright © 2016 Elsevier Inc. All rights reserved.
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)
Serum cholinesterase polymorphism (CHE1 and CHE2 loci) among several Indian groups from Amazon region of Brazil, and segregation of the C5 variant in families.

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Guerreiro, J F; Santos, S E; Aguiar, G F

1989-04-01

Eight Indian tribes from the Amazon region of Brazil (Araweté, Arara, Yamamadi, Kararaô, Karitiana, Waiampi, Surui and Cinta Larga) were studied for the distribution of the atypical and C5 variants of serum cholinesterase. None of them presented the CHE1*A allele, but the C5 variant was found in the Araweté (20.4%), Kararaô (15.6%), Karitiana (50.5%), Surui (12.3%) and Cinta Larga (19.6%) tribes. The frequency of the C5+ phenotype in the Karitiana is the highest reported thus far in human populations. Segregation studies considering the C5 variant were made among the Karitiana, and also among the Urubu-Kaapor and Munduruku tribes previously studied by Guerreiro et al [1987a, 1987b]. Most of the data were in agreement with the genetic hypothesis, but they also revealed a significant lack of the C5+ phenotype in offspring from C5+ X C5+ matings, as well as the occurrence of two C5+ children from C5- X C5- unions, in the Urubu-Kaapor tribe.
In-vitro Antioxidant, Cytotoxic, Cholinesterase Inhibitory Activities and Anti-Genotoxic Effects of Hypericum retusum Aucher Flowers, Fruits and Seeds Methanol Extracts in Human Mononuclear Leukocytes.

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Keskin, Cumali; Aktepe, Necmettin; Yükselten, Yunus; Sunguroglu, Asuman; Boğa, Mehmet

2017-01-01

The present study investigates the antioxidant, anticancer, anticholinesterase, anti-genotoxic activities and phenolic contents of flower, fruit and seed methanol extracts of Hypericum retusum AUCHER. The amounts of protocatechuic acid, catechin, caffeic acid and syringic acid in methanol extracts were determined by HPLC. Total phenolic content of H. retusum seed extract was found more than fruit and flower extracts. The DPPH free radical scavenging activity of flower and seed methanol extracts showed close activity versus BHT as control. Among three extracts of H. retusum only flower methanol extract was exhibited considerable cytotoxic activities against to HeLa and NRK-52E cell lines. Moreover, seed methanol extract showed both acetyl and butyrl-cholinesterase inhibitory activity. The highest anti-genotoxic effects were seen 25 and 50 μg/mL concentrations. In this study, the extracts showed a strong antioxidant and anti-genotoxic effect. The seed extract was more efficient- than extracts of fruit and flowers. Our results suggest that the antioxidant and anti-genotoxic effects of extracts depend on their phenolic contents. Further studies should evaluate the in-vitro and in-vivo the benefits of H. retusum seed methanol extracts.
Natural Detoxification Capacity to Inactivate Nerve Agents Sarin and VX in the Rat Blood

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Jiří Bajgar

2016-03-01

Full Text Available Background: The method of continual determination of the rat blood cholinesterase activity was developed to study the changes of the blood cholinesterases following different intervetions. Aims: The aim of this study is registration of cholinesterase activity in the rat blood and its changes to demonstrate detoxification capacity of rats to inactivate sarin or VX in vivo. Methods: The groups of female rats were premedicated (ketamine and xylazine and cannulated to a. femoralis. Continual blood sampling (0.02 ml/min and monitoring of the circulating blood cholinesterase activity were performed. Normal activity was monitored 1–2 min and then the nerve agent was administered i.m. (2× LD50. Using different time intervals of the leg compression and relaxation following the agent injection, cholinesterase activity was monitored and according to the inhibition obtained, detoxification capacity was assessed. Results: Administration of sarin to the leg, then 1 and 5 min compression and 20 min later relaxation showed that further inhibition in the blood was not observed. On the other hand, VX was able to inhibit blood cholinesterases after this intervention. Conclusions: The results demonstrated that sarin can be naturally detoxified on the contrary to VX. Described method can be used as model for other studies dealing with changes of cholinesterases in the blood following different factors.
Experimental chemotherapy of Schistosomiasis III: laboratory and clinical trials with trichlorphone, an organophosphorus compound

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Naftale Katz

1968-10-01

Full Text Available Oogram studies have been carried out on mice, hamsters, and Cebus morikeys experimentally infected with Schistosoma mansoni and treated with trichlorphone (0,0-dimethyl 1-hydroxy-2, 2, 2-trichloroethylphosphonate. In mice, despite a slight hepatic shift of schistosomes, all animais presented oogram changes when dosed, per os, at the schedules of 200, and 100 mg/kg/day × 7. In hamsters, antischistosomal activity could be detected only at toxic leveis. In monkeys, trichlorphone showed insignificant action even after oral administration of 30 mg/kg/day for 10 consecutive days. In 5 volunteers, a sharp drop in cholinesterase plasma level was observed 24 hours after a single oral dose of 7.5 mg/kg. However, cholinesterase levels returned to the initial values within a period of 11 to 27 days. Trichlorphone was then administered to 12 schistosome patients (7.5 mg/kg/day, every fort- night, × 5. One month after therapy, interruption of egg laying was observed in 6 patients. Late parasitological control showed that all treated patients continued to pass viable S. mansoni eggs with their stools.
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
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.
PENCEGAHAN EFEK PESTISIDA PADA PETANI DI DESA BUAHAN KINTAMANI

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I MADE SUTARGA

2012-09-01

Full Text Available Abtract In the year 2004 from the result of research of horticultura farmer, from 46 person who had been checked their blood cholinesterase found 17.4% suffering of poison pesticide, 56.5% their knowlage still less to manage pesticide and also 47.8% less behavior in conducting real correct spraying, self protector applied should be used. The purpose of this activity to give understanding to farmer that use pesticide in managing pesticide and also to see pesticide conten through inspection of periodical cholinesterase. On Oktober 2006 from result checking of cholinesterase enzyme from 39 farmers. Their blood sample found cholinesterase enzyme rate >50-75 with degradation egual to 25% or suffer light poisond equal 23%. Farmer behavior in using pesticide still less. That is why counselling and also society inspection of cholinesterase enzyme required to be level and in the event of poisoned hence require to be intervenced continually through counselling continually through counselling and is rejancent of society.
PREVENTING EFFECT OF THE PESTICIDE IN FARMING SOCIETY AT BUAHAN VILLAGE, KINTAMANI, BANGLI

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dr. I Made Sutarga

2012-09-01

Full Text Available Abtract In the year 2004 from the result of research of horticultura farmer, from 46 person who had been checked their blood cholinesterase found 17.4% suffering of poison pesticide, 56.5% their knowlage still less to manage pesticide and also 47.8% less behavior in conducting real correct spraying, self protector applied should be used. The purpose of this activity to give understanding to farmer that use pesticide in managing pesticide and also to see pesticide conten through inspection of periodical cholinesterase. On Oktober 2006 from result checking of cholinesterase enzyme from 39 farmers. Their blood sample found cholinesterase enzyme rate >50-75 with degradation egual to 25% or suffer light poisond equal 23%. Farmer behavior in using pesticide still less. That is why counselling and also society inspection of cholinesterase enzyme required to be level and in the event of poisoned hence require to be intervenced continually through counselling continually through counselling and is rejancent of society.
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, 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
Multitarget Therapeutic Leads for Alzheimer's Disease: Quinolizidinyl Derivatives of Bi- and Tricyclic Systems as Dual Inhibitors of Cholinesterases and β-Amyloid (Aβ) Aggregation.

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Tonelli, Michele; Catto, Marco; Tasso, Bruno; Novelli, Federica; Canu, Caterina; Iusco, Giovanna; Pisani, Leonardo; Stradis, Angelo De; Denora, Nunzio; Sparatore, Anna; Boido, Vito; Carotti, Angelo; Sparatore, Fabio

2015-06-01

Multitarget therapeutic leads for Alzheimer's disease were designed on the models of compounds capable of maintaining or restoring cell protein homeostasis and of inhibiting β-amyloid (Aβ) oligomerization. Thirty-seven thioxanthen-9-one, xanthen-9-one, naphto- and anthraquinone derivatives were tested for the direct inhibition of Aβ(1-40) aggregation and for the inhibition of electric eel acetylcholinesterase (eeAChE) and horse serum butyrylcholinesterase (hsBChE). These compounds are characterized by basic side chains, mainly quinolizidinylalkyl moieties, linked to various bi- and tri-cyclic (hetero)aromatic systems. With very few exceptions, these compounds displayed inhibitory activity on both AChE and BChE and on the spontaneous aggregation of β-amyloid. In most cases, IC50 values were in the low micromolar and sub-micromolar range, but some compounds even reached nanomolar potency. The time course of amyloid aggregation in the presence of the most active derivative (IC50 =0.84 μM) revealed that these compounds might act as destabilizers of mature fibrils rather than mere inhibitors of fibrillization. Many compounds inhibited one or both cholinesterases and Aβ aggregation with similar potency, a fundamental requisite for the possible development of therapeutics exhibiting a multitarget mechanism of action. The described compounds thus represent interesting leads for the development of multitarget AD therapeutics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Association between arsenic exposure and plasma cholinesterase activity: a population based study in Bangladesh

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Karim Md Rezaul

2010-07-01

Full Text Available Abstract Background Arsenic is a potent pollutant that has caused an environmental catastrophe in certain parts of the world including Bangladesh where millions of people are presently at risk due to drinking water contaminated by arsenic. Chronic arsenic exposure has been scientifically shown as a cause for liver damage, cancers, neurological disorders and several other ailments. The relationship between plasma cholinesterase (PChE activity and arsenic exposure has not yet been clearly documented. However, decreased PChE activity has been found in patients suffering liver dysfunction, heart attack, cancer metastasis and neurotoxicity. Therefore, in this study, we evaluated the PChE activity in individuals exposed to arsenic via drinking water in Bangladesh. Methods A total of 141 Bangladeshi residents living in arsenic endemic areas with the mean arsenic exposure of 14.10 ± 3.27 years were selected as study subjects and split into tertile groups based on three water arsenic concentrations: low ( 265 μg/L. Study subjects were further sub-divided into two groups (≤50 μg/L and > 50 μg/L based on the recommended upper limit of water arsenic concentration (50 μg/L in Bangladesh. Blood samples were collected from the study subjects by venipuncture and arsenic concentrations in drinking water, hair and nail samples were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS. PChE activity was assayed by spectrophotometer. Results Arsenic concentrations in hair and nails were positively correlated with the arsenic levels in drinking water. Significant decreases in PChE activity were observed with increasing concentrations of arsenic in water, hair and nails. The average levels of PChE activity in low, medium and high arsenic exposure groups were also significantly different between each group. Lower levels of PChE activity were also observed in the > 50 μg/L group compared to the ≤50 μg/L group. Moreover, PChE activity was
Cost-utility analysis of memantine extended release added to cholinesterase inhibitors compared to cholinesterase inhibitor monotherapy for the treatment of moderate-to-severe dementia of the Alzheimer's type in the US.

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Saint-Laurent Thibault, Catherine; Özer Stillman, Ipek; Chen, Stephanie; Getsios, Denis; Proskorovsky, Irina; Hernandez, Luis; Dixit, Shailja

2015-01-01

This study evaluates the cost-effectiveness of memantine extended release (ER) as an add-on therapy to acetylcholinesterase inhibitor (AChEI) [combination therapy] for treatment of patients with moderate-to-severe Alzheimer's disease (AD) from both a healthcare payer and a societal perspective over 3 years when compared to AChEI monotherapy in the US. A phase III trial evaluated the efficacy and safety of memantine ER for treatment of AD patients taking an AChEI. The analysis assessed the long-term costs and health outcomes using an individual patient simulation in which AD progression is modeled in terms of cognition, behavior, and functioning changes. Input parameters are based on patient-level trial data, published literature, and publicly available data sources. Changes in anti-psychotic medication use are incorporated based on a published retrospective cohort study. Costs include drug acquisition and monitoring, total AD-related medical care, and informal care associated with caregiver time. Incremental cost-utility ratio (ICUR), life years, care time for caregiver, time in community and institution, time on anti-psychotics, time by disease severity, and time without severe symptoms are reported. Costs and health outcomes are discounted at 3% per annum. Considering a societal perspective over 3 years, this analysis shows that memantine ER combined with an AChEI provides better clinical outcomes and lower costs than AChEI monotherapy. Discounted average savings were estimated at $18,355 and $20,947 per patient and quality-adjusted life-years (QALYs) increased by an average of 0.12 and 0.13 from a societal and healthcare payer perspective, respectively. Patients on combination therapy spent an average of 4 months longer living at home and spend less time in moderate-severe and severe stages of the disease. Combination therapy for patients with moderate-to-severe AD is a cost-effective treatment compared to AChEI monotherapy in the US.
Fabrication of magnetic and fluorescent chitin and dibutyrylchitin sub-micron particles by oil-in-water emulsification.

Science.gov (United States)

Blanco-Fernandez, Barbara; Chakravarty, Shatadru; Nkansah, Michael K; Shapiro, Erik M

2016-11-01

Chitin is a carbohydrate polymer with unique pharmacological and immunological properties, however, because of its unwieldy chemistry, the synthesis of discreet sized sub-micron particles has not been well reported. This work describes a facile and flexible method to fabricate biocompatible chitin and dibutyrylchitin sub-micron particles. This technique is based on an oil-in-water emulsification/evaporation method and involves the hydrophobization of chitin by the addition of labile butyryl groups onto chitin, disrupting intermolecular hydrogen bonds and enabling solubility in the organic solvent used as the oil phase during fabrication. The subsequent removal of butyryl groups post-fabrication through alkaline saponification regenerates native chitin while keeping particles morphology intact. Examples of encapsulation of hydrophobic dyes and nanocrystals are demonstrated, specifically using iron oxide nanocrystals and coumarin 6. The prepared particles had diameters between 300-400nm for dibutyrylchitin and 500-600nm for chitin and were highly cytocompatible. Moreover, they were able to encapsulate high amounts of iron oxide nanocrystals and were able to label mammalian cells. We describe a technique to prepare sub-micron particles of highly acetylated chitin (>90%) and dibutyrylchitin and demonstrate their utility as carriers for imaging. Chitin is a polysaccharide capable of stimulating the immune system, a property that depends on the acetamide groups, but its insolubility limits its use. No method for sub-micron particle preparation with highly acetylated chitins have been published. The only approach for the preparation of sub-micron particles uses low acetylation chitins. Dibutyrylchitin, a soluble chitin derivative, was used to prepare particles by oil in water emulsification. Butyryl groups were then removed, forming chitin particles. These particles could be suitable for encapsulation of hydrophobic payloads for drug delivery and cell imaging, as well as

Polyketide synthases from poison hemlock (Conium maculatum L.).

Science.gov (United States)

Hotti, Hannu; Seppänen-Laakso, Tuulikki; Arvas, Mikko; Teeri, Teemu H; Rischer, Heiko

2015-11-01

Coniine is a toxic alkaloid, the biosynthesis of which is not well understood. A possible route, supported by evidence from labelling experiments, involves a polyketide formed by the condensation of one acetyl-CoA and three malonyl-CoAs catalysed by a polyketide synthase (PKS). We isolated PKS genes or their fragments from poison hemlock (Conium maculatum L.) by using random amplification of cDNA ends (RACE) and transcriptome analysis, and characterized three full-length enzymes by feeding different starter-CoAs in vitro. On the basis of our in vitro experiments, two of the three characterized PKS genes in poison hemlock encode chalcone synthases (CPKS1 and CPKS2), and one encodes a novel type of PKS (CPKS5). We show that CPKS5 kinetically favours butyryl-CoA as a starter-CoA in vitro. Our results suggest that CPKS5 is responsible for the initiation of coniine biosynthesis by catalysing the synthesis of the carbon backbone from one butyryl-CoA and two malonyl-CoAs. © 2015 FEBS.
Eye-related visual hallucinations: Consider ′Charles Bonnet syndrome′

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Nilgun Cinar

2011-01-01

Full Text Available The Charles Bonnet Syndrome (CBS is typically characterized by visual hallucinations in elderly people without cognitive defects. This article presents the case of an 80-year-old male patient with a one-year history of visual hallucinations, secondary to glaucoma, in both eyes. Neither a dopamine agonist nor cholinesterase inhibitor therapy improved his symptoms. In this case, the hallucinations were gradually improved after administration of a GABAergic drug, pregabalin, for diabetic polyneuropathy. Placebo-controlled clinical trials would be needed to support this effect of pregabalin, as suggested by this association.
Inhibition of cholinesterase activity by extracts, fractions and compounds from Calceolaria talcana and C. integrifolia (Calceolariaceae: Scrophulariaceae).

Science.gov (United States)

Cespedes, Carlos L; Muñoz, Evelyn; Salazar, Juan R; Yamaguchi, Lydia; Werner, Enrique; Alarcon, Julio; Kubo, Isao

2013-12-01

Extracts, fractions and compounds from Calceolaria talcana and C. integrifolia exhibited strong inhibitory effects of the activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes using the in vitro Ellman's method. The most active samples were from the ethyl acetate extract, which caused a mixed-type inhibition against AChE (69.8% and 79.5% at 100 and 200 μg/ml, respectively) and against BChE (98.5% and 99.8% at 100 and 200 μg/ml, respectively) and its major components verbascoside 8 (50.9% and 70.0% at 200 μg/ml, against AChE and BChE, respectively), martynoside 9, and fraction F-7 (which corresponds to a mixture of 8, 9, and other phenylethanoids and phenolics that remain unidentified) (80.2% and 85.3% at 100 and 200 μg/ml, against AChE, respectively and 99.1% and 99.7% at 100 and 200 μg/ml, against BChE, respectively) inhibited the acetylcholinesterase enzyme competitively. The most polar fraction F-5 from n-hexane extract (a mixture of naphthoquinones: 2-hydroxy-3-(1,1-dimethylallyl-1,4-naphthoquinone) 6, α-dunnione 7 and other polar compounds that remain unidentified) showed a mixed-type inhibition (71.5% and 72.1% against AChE and BChE at 200 μg/ml, respectively). Finally, the methanol-soluble residue presented a complex, mixed-type inhibition (39.9% and 67.9% against AChE and BChE at 200 μg/ml, respectively). The mixture F-3 with diterpenes was obtained from the n-hexane extract: (1,10-cyclopropyl-9-epi-ent-isopimarol) 1, 19-α-hydroxy-abietatriene 2, and F-4 a mixture of triterpenes α-lupeol 3, β-sitosterol 4, ursolic acid 5 together with a complex mixture of terpenes that did not show activity. In summary, extracts and natural compounds from C. talcana and C. integrifolia were isolated, identified and characterized as cholinesterase inhibitors.
Muscarinic receptors as targets for anti-inflammatory therapy.

Science.gov (United States)

Sales, María Elena

2010-11-01

ACh, the main neurotransmitter in the neuronal cholinergic system, is synthesized by pre-ganglionic fibers of the sympathetic and parasympathetic autonomic nervous system and by post-ganglionic parasympathetic fibers. There is increasing experimental evidence that ACh is widely expressed in prokaryotic and eukaryotic non-neuronal cells. The neuronal and non-neuronal cholinergic systems comprise ACh, choline acetyltransferase and cholinesterase, enzymes that synthesize and catabolize ACh, and the nicotinic and muscarinic ACh receptors (nAChRs and mAChRs, respectively), which are the targets for ACh action. This review analyzes the participation of the cholinergic system, particularly through mAChRs, in inflammation, and discusses the role of the different mAChR antagonists that have been used to treat skin inflammatory disorders, asthma and COPD, as well as intestinal inflammation and systemic inflammatory diseases, to assess the potential application of these compounds as therapeutic tools.
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.
Pterostilbene-O-acetamidoalkylbenzylamines derivatives as novel dual inhibitors of cholinesterase with anti-β-amyloid aggregation and antioxidant properties for the treatment of Alzheimer's disease.

Science.gov (United States)

Li, Yuxing; Qiang, Xiaoming; Li, Yan; Yang, Xia; Luo, Li; Xiao, Ganyuan; Cao, Zhongcheng; Tan, Zhenghuai; Deng, Yong

2016-04-15

A series of pterostilbene-O-acetamidoalkylbenzylamines were designed, synthesized and evaluated as dual inhibitors of AChE and BuChE. To further explore the multifunctional properties of the new derivatives, their antioxidant activities and inhibitory effects on self-induced Aβ1-42 aggregation and HuAChE-induced Aβ1-40 aggregation were also tested. The results showed that most of these compounds could effectively inhibit AChE and BuChE. Particularly, compound 21d exhibited the best AChE inhibitory activity (IC50=0.06 μM) and good inhibition of BuChE (IC50=28.04 μM). Both the inhibition kinetic analysis and molecular modeling study revealed that these compounds showed mixed-type inhibition, binding simultaneously to the CAS and PAS of AChE. In addition to cholinesterase inhibitory activities, these compounds showed different levels of antioxidant activity. However, the inhibitory activities against self-induced and HuAChE-induced Aβ aggregation of these new derivatives were unsatisfied. Taking into account the results of the biological evaluation, further modifications will be designed in order to increase the potency on the different targets. The results displayed in this Letter can be a new starting point for further development of multifunctional agents for Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.
A Method for Fast Assessment of OP/CB Exposure in the Japanese Quail (Coturnix coturnix japonica Using Combined Esterases Enzyme Activity as Biomarkers

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Kasim Sakran Abass

2014-01-01

Full Text Available The aims of this study were to investigate the presence of different esterase activities in plasma and liver for Japanese quail and to combine determination of both carboxylesterase and cholinesterase as biochemical biomarker in order to identify the effects of carbamate and organophosphate compounds exposure. Carboxylesterase exhibits larger sensitivity to carbamate and organophosphate compounds than to cholinesterase and is present at higher levels. This permitted nature and distribution of carboxylesterase or cholinesterase to be measured. One predominant toxicological form of enzyme level constant in its patterns of motivation and inhibition with cholinesterase was identified in plasma with an apparent Michaelis constant for butyrylthiocholine iodide of 0.394 mM. Carboxylesterase activity in liver was considered by its preferential hydrolysis of the S-phenyl thioacetate. A concentration dependent decrease of carboxylesterase and cholinesterase has demonstrated during in vitro incubation of malathion, parathion, and trichlorfon in the range 0.125–2 mM, while with methomyl was in the range 0.25–4 mM. When quail (n=15 was exposed orally for 48 h to concentrations of carbamate or organophosphate compounds of 3–200 mg/kg, the percentage inhibition of cholinesterase was in each case larger than that of carboxylesterase and reached statistical significance (P<0.05 at lower concentrations.
Pharmacokinetics and pharmacodynamics of mivacurium in young adult and elderly patients

DEFF Research Database (Denmark)

Østergaard, Doris; Viby-Mogensen, Jørgen; Pedersen, N.A.

2002-01-01

age factors; butyrylcholinesterase; cholinesterase; dose-response curves; enzymes; metabolites; mivacurium; neuromuscular relaxants; pharmacodynamics; pharmacokinetics; pharmacology; pseudocholinesterase; stereoisomers......age factors; butyrylcholinesterase; cholinesterase; dose-response curves; enzymes; metabolites; mivacurium; neuromuscular relaxants; pharmacodynamics; pharmacokinetics; pharmacology; pseudocholinesterase; stereoisomers...
[Therapy-resistant and therapy-refractory arterial hypertension].

Science.gov (United States)

Wallbach, M; Koziolek, M J

2018-05-02

Therapy-resistant and therapy-refractory arterial hypertension differ in prevalence, pathogenesis, prognosis and therapy. In both cases, a structured approach is required, with the exclusion of pseudoresistance and, subsequently, secondary hypertension. Resistant hypertension has been reported to be more responsive to intensified diuretic therapy, whereas refractory hypertension is presumed to require sympathoinhibitory therapy. Once the general measures and the drug-based step-up therapy have been exhausted, interventional procedures are available.
Art Therapy: What Is Art Therapy?

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... individual, couples, family, and group therapy formats. Art therapy is an effective treatment for people experiencing developmental, medical, educational, and social or psychological impairment. Individuals who benefit from art therapy include ...
Acylated ghrelin concentrations are markedly decreased during pregnancy in mothers with and without gestational diabetes: relationship with cholinesterase.

Science.gov (United States)

Tham, Elaine; Liu, Jianhua; Innis, Sheila; Thompson, David; Gaylinn, Bruce D; Bogarin, Roberto; Haim, Alon; Thorner, Michael O; Chanoine, Jean-Pierre

2009-05-01

Acylated (octanoylated) ghrelin stimulates food intake and growth hormone secretion and is deacylated into desacyl ghrelin by butyrylcholinesterase. Acylated and desacyl ghrelin both promote adipogenesis. Ghrelin concentrations decrease with hyperglycemia and hyperinsulinism. We hypothesized that 1) acylated ghrelin increases during pregnancy, contributing positively to energy balance, but is lower in women with gestational diabetes and 2) butyrylcholinesterase activity is inversely correlated with acylated ghrelin concentrations. In a first group of subjects, using two-site sandwich ghrelin assays that specifically detect full-length forms, we investigated women with and without gestational diabetes (n = 14/group) during pregnancy and after delivery. We examined whether changes in ghrelin during a test meal were correlated with changes in pituitary growth hormone [assessed through calculation of the area under the curve (AUC) during the test meal]. In postpartum subjects, the percent of total ghrelin that is acylated was four to five times higher than previously observed using single antibody assays. During pregnancy, acylated ghrelin concentrations (mean +/- SE) were lower compared with the postpartum period throughout the meal (AUC 1.2 +/- 0.2 vs. 10.2 +/- 1.9 ng.ml(-1).90 min(-1), P < 0.001). In the postpartum, acylated ghrelin and growth hormone were positively correlated (r = 0.50, P = 0.007). Desacyl (but not acylated) ghrelin was increased in subjects with gestational diabetes during and after pregnancy (AUC 15.4 +/- 1.9 vs. 8.6 +/- 1.2 ng.ml(-1).90 min(-1), P = 0.005). In a second group of subjects (n = 13), acylated ghrelin was similarly suppressed during pregnancy. Circulating octanoate concentrations (3.1 +/- 0.5 vs. 4.5 +/- 0.6 microg/ml, P = 0.029) and cholinesterase activity (705 +/- 33 vs. 1,013 +/- 56 U/ml, P < 0.001) were lower during pregnancy compared with the postpartum period. In conclusion, acylated ghrelin markedly decreases during pregnancy
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.
75 FR 50880 - TRICARE: Non-Physician Referrals for Physical Therapy, Occupational Therapy, and Speech Therapy

Science.gov (United States)

2010-08-18

... 0720-AB36 TRICARE: Non-Physician Referrals for Physical Therapy, Occupational Therapy, and Speech... referrals of beneficiaries to the Military Health System for physical therapy, occupational therapy, and... practitioners will be allowed to issue referrals to patients for physical therapy, occupational therapy, and...
LAMA PAJANAN ORGANOFOSFAT TERHADAP PENURUNAN AKTIVITAS ENZIM KOLINESTERASE DALAM DARAH PETANI SAYURAN

Directory of Open Access Journals (Sweden)

Dewi Susanna

2010-12-01

Full Text Available Organophosphate Pesticide Exposure Effects toward Inhibition of Blood Cholinesterase Activity among Vegetable Farmers. Organophosphate pesticides can inhibit blood cholinesterase in human body. This study aimed to find relationship between length of exposure of organophosphate pesticides with cholinesterase enzyme activity in the farmers’ blood. The study was conducted at the Joint Farmers Group in Kelurahan Campang year 2009 using cross-sectional study design and sampling by the simple random sampling method (56 respondents. Data collection was carried out by interview and blood cholinesterase was measured using the Livibond Cholinesterase Test Kit AF267. Results showed that 100% farmers were poisoned, with 71.4% suffer from light-over-exposure and 28.6% moderate-over exposure. Bivariate test analysis using chi-square test showed that there are no statistically significant relationship between the length of exposure (year of working as pesticide farmer, spraying time per week, and the last time spraying with poisoning level (over-exposure probable and serious-over exposure. It takes the role of government to educate and trained farmers how to use pesticide safely and the importance of personal protective equipment to reduce the poisoning level.
Joint Service Chemical and Biological Defense Program: FY 06-07 Overview

Science.gov (United States)

2006-01-01

Performers Molecular model of human plasma-derived butyryl Electronmicrograph of bacillus spores adhering to cell membrane processes 38866_BATT_TX 11...agents, and radioactive fallout. CPS is integrated with the ship’s Heating, Ventilation, and Air-Conditioning ( HVAC ) systems and provides filtered air...molecules for intervention against protein NTA. • Identify and evaluate effectiveness of spore germination inhibitors. • Expand drug discovery program
Recent Advances in the Treatment of Organophosphorous Poisonings

Directory of Open Access Journals (Sweden)

Mahdi Balali-Mood

2012-06-01

Full Text Available Organophosphorous compounds have been employed as pesticides and chemical warfare nerve agents. Toxicity of organophosphorous compounds is a result of excessive cholinergic stimulation through inhibition of acetyl cholinesterase. Clinical manifestations include cholinergic syndromes, central nervous system and cardiovascular disorders. Organophosphorous pesticide poisonings are common in developing worlds including Iran and Sri Lanka. Nerve agents were used during the Iraq-Iran war in 1983-1988 and in a terrorist attack in Japan in 1994-1995. Following decontamination, depending on the severity of intoxication the administration of atropine to counteract muscarinic over-stimulation, and an oxime to reactivate acetyl cholinesterase are indicated. Supportive and intensive care therapy including diazepam to control convulsions and mechanical respiration may be required. Recent investigations have revealed that intravenous infusion of sodium bicarbonate to produce mild to moderate alkalinization is effective. Gacyclidine; an antiglutamatergic compound, was also proved to be beneficial in conjunction with atropine, pralidoxime, and diazepam in nerve agent poisoning. Intravenous magnesium sulfate decreased hospitalization duration and improved outcomes in patients with organophosphorous poisoning. Bio-scavengers including fresh frozen plasma or albumin have recently been suggested as a useful therapy through clearing of free organophosphates. Hemofiltration and antioxidants are also suggested for organophosphorous poisoning. Recombinant bacterial phosphotriesterases and hydrolases that are able to transfer organophosphorous-degrading enzymes are very promising in delayed treatment of organophosphorous poisoning. Recently, encapsulation of drugs or enzymes in nanocarriers has also been proposed. Given the signs and symptoms of organophosphorous poisoning, health professionals should remain updated about the recent advances in treatment of
Recent Advances in the Treatment of Organophosphorous Poisonings

Science.gov (United States)

Balali-Mood, Mahdi; Saber, Hamidreza

2012-01-01

Organophosphorous compounds have been employed as pesticides and chemical warfare nerve agents. Toxicity of organophosphorous compounds is a result of excessive cholinergic stimulation through inhibition of acetyl cholinesterase. Clinical manifestations include cholinergic syndromes, central nervous system and cardiovascular disorders. Organophosphorous pesticide poisonings are common in developing worlds including Iran and Sri Lanka. Nerve agents were used during the Iraq-Iran war in 1983-1988 and in a terrorist attack in Japan in 1994-1995. Following decontamination, depending on the severity of intoxication the administration of atropine to counteract muscarinic over-stimulation, and an oxime to reactivate acetyl cholinesterase are indicated. Supportive and intensive care therapy including diazepam to control convulsions and mechanical respiration may be required. Recent investigations have revealed that intravenous infusion of sodium bicarbonate to produce mild to moderate alkalinization is effective. Gacyclidine; an antiglutamatergic compound, was also proved to be beneficial in conjunction with atropine, pralidoxime, and diazepam in nerve agent poisoning. Intravenous magnesium sulfate decreased hospitalization duration and improved outcomes in patients with organophosphorous poisoning. Bio-scavengers including fresh frozen plasma or albumin have recently been suggested as a useful therapy through clearing of free organophosphates. Hemofiltration and antioxidants are also suggested for organophosphorous poisoning. Recombinant bacterial phosphotriesterases and hydrolases that are able to transfer organophosphorous-degrading enzymes are very promising in delayed treatment of organophosphorous poisoning. Recently, encapsulation of drugs or enzymes in nanocarriers has also been proposed. Given the signs and symptoms of organophosphorous poisoning, health professionals should remain updated about the recent advances in treatment of organophosphorous poisoning
Distribution and substrate specificity of esterases in the housefly, Musca domestica L.

NARCIS (Netherlands)

Asperen, K. van

1959-01-01

Housefly homogenates perform high cholinesterase and ali-esterase activity. Warburg-manometric studies show that acetylcholine, acetyl-β-methylcholine, butyrylcholine, and benzoylcholine are exclusively hydrolysed by a cholinesterase, the properties of which are more or less comparable to those of
Stabilizing Acetylcholinesterase on Carbon Electrodes Using Peptide Nanotubes to Produce Effective Biosensors

Science.gov (United States)

2012-03-22

disposable, inhibition 1. Introduction Organophosphates (OPs) are acetyl cholinesterase (AChE) inhibitors with a broad range of potency and toxicity...5 Cholinesterase Biosensors...BIOSENSORS I. Introduction Background Organophosphates (OPs) are acetylcholinesterase (AChE) inhibitors with a broad range of potency and
Humanistic therapies versus other psychological therapies for depression

Science.gov (United States)

Churchill, Rachel; Davies, Philippa; Caldwell, Deborah; Moore, Theresa HM; Jones, Hannah; Lewis, Glyn; Hunot, Vivien

2014-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: To examine the effectiveness and acceptability of all humanistic therapies compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of different humanistic therapy models (person-centred, gestalt, process-experiential, transactional analysis, existential and non-directive therapies) compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of all humanistic therapies compared with different psychological therapy approaches (psychodynamic, behavioural, humanistic, integrative, cognitive-behavioural) for acute depression. PMID:25278809

Gene therapy and radionuclides targeting therapy in mammary carcinoma

International Nuclear Information System (INIS)

Song Jinhua

2003-01-01

Breast carcinoma's gene therapy is a hotspot in study of the tumor's therapy in the recent years. Currently the major therapy methods that in the experimentative and primary clinical application phases include immunological gene therapy, multidrug resistance gene therapy, antisense oligonucleotide therapy and suicide gene therapy. The gene targeting brachytherapy, which is combined with gene therapy and radiotherapy has enhanced the killer effects of the suicide gene and nuclide in tumor cells. That has break a new path in tumor's gene therapy. The further study in this field will step up it's space to the clinical application
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.
Intensity-modulated radiation therapy: dynamic MLC (DMLC) therapy, multisegment therapy and tomotherapy. An example of QA in DMLC therapy

International Nuclear Information System (INIS)

Webb, S.

1998-01-01

Intensity-modulated radiation therapy will make a quantum leap in tumor control. It is the new radiation therapy for the new millennium. The major methods to achieve IMRT are: 1. Dynamic multileaf collimator (DMLC) therapy, 2. multisegment therapy, and 3. tomotherapy. The principles of these 3 techniques are briefly reviewed. Each technique presents unique QA issues which are outlined. As an example this paper will present the results of a recent new study of an important QA concern in DMLC therapy. (orig.) [de
75 FR 56101 - FIFRA Scientific Advisory Panel; Notice of Rescheduled Public Meeting

Science.gov (United States)

2010-09-15

... pesticides, cholinesterase inhibition, data-derived uncertainty factors (also referred to as chemical..., sources of research support. EPA will evaluate the candidates financial disclosure form to assess whether... was largely based on adult laboratory animal data (rat or dog) for cholinesterase inhibition and the...
Acetylcholinesterase concentrations in heparinized blood of Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Tully, Thomas N; Osofsky, Anna; Jowett, Peter L H; Hosgood, Giselle

2003-12-01

Organophosphate and carbamate pesticides inhibit acetylcholinesterase (AChE) at nerve synapses. Blood samples from 22 Hispaniolan Amazon parrots (Amazona ventralis) were assayed for cholinesterase levels by two different techniques. Using the modified Michel method, the whole-blood cholinesterase activity levels ranged from 0.082 to 0.616 deltapH/hr with a mean value of 0.35 deltapH/hr. A reference range (0.08-0.62 deltapH/hr) for cholinesterase was established in birds. The modified Ellman spectrophotometric method was used to measure AChE activity by adding acetylthiocholine or pseudocholinesterase (plasma cholinesterase) activity by adding butyrylthiocholine. The reference range of the AChE activity using the modified Ellman spectrophotometric method was 0-1.12 micromol/ml/min with a mean of 0.48 micromol/ml/min, and for pseudocholinesterase the range was 0.09-0.98 micromol/ml/min with a mean of 0.53 micromol/ml/min.
Physical Therapy and Occupational Therapy in Progeria

Science.gov (United States)

Physical Therapy and Occupational Therapy in Progeria Information for Families and Caretakers from The Progeria Research Foundation ... Inc. All rights reserved. Page 2 of 5 Physical and Occupational Therapy in Progeria Hutchinson-Gilford Progeria ...
Cardiale neveneffecten van cholinesteraseremmers : een reden tot terughoudendheid in voorschrijven?

NARCIS (Netherlands)

Salarbaks, A M; Boomkamp-Snoeren, C M; van Puijenbroek, E; Jansen, P A F; van Marum, R J

Cholinesterase inhibitors are prescribed in the treatment of mild to moderate Alzheimer's dementia. Little is known about the cardiac safety of these drugs. We present two different cases in which cardiac events occurred during the use of a cholinesterase inhibitor. The pathophysiology, the effects
Time course of cholinesterase inhibition in adult rats treated acutely with carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl or propoxur

International Nuclear Information System (INIS)

Padilla, S.; Marshall, R.S.; Hunter, D.L.; Lowit, A.

2007-01-01

To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n = 4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); carbofuran (0.5 mg/kg in corn oil); formetanate HCl (10 mg/kg in water); methomyl (3 mg/kg in water); methiocarb (25 mg/kg in corn oil); oxamyl (1 mg/kg in water); or propoxur (20 mg/kg in corn oil). This level of dosing produced at least 40% brain ChE inhibition. Brain and blood were taken from 0.5 to 24 h after dosing for analysis of ChE activity using two different methods: (1) a radiometric method which limits the amount of reactivation of ChE activity, and (2) a spectrophotometric method (Ellman method using traditional, unmodified conditions) which may encourage reactivation. The time of peak ChE inhibition was similar for all seven N-methyl carbamate pesticides: 0.5-1.0 h after dosing. By 24 h, brain and RBC ChE activity in all animals returned to normal. The spectrophotometric method underestimated ChE inhibition. Moreover, there was a strong, direct correlation between brain and RBC ChE activity (radiometric assay) for all seven compounds combined (r 2 = 0.73, slope 1.1), while the spectrophotometric analysis of the same samples showed a poor correlation (r 2 = 0.09). For formetanate, propoxur, methomyl, and methiocarb, brain and RBC ChE inhibitions were not different over time, but for carbaryl, carbofuran and oxamyl, the RBC ChE was slightly more inhibited than brain ChE. These data indicate (1) the radiometric method is superior for analyses of ChE activity in tissues from carbamate-treated animals (2) that animals treated with these N-methyl carbamate pesticides are affected rapidly, and recover rapidly, and (3) generally, assessment of RBC ChE is an accurate predictor of brain ChE inhibition for these seven pesticides
Gestalt Therapy and Cognitive Therapy - Contrasts or Complementarities?

DEFF Research Database (Denmark)

Tønnesvang, Jan; Sommer, Ulla; Hammink, James

2010-01-01

The article investigates the relationship between crucial concepts and understandings in gestalt therapy and cognitive therapy aiming at discussing if and how they can be mutually enriching when considered as complementary parts in a more encompassing integrative therapeutic approach. It is argued...... that gestalt therapy, defined as a fieldtheoretical approach to the study of gestalt formation process, can complement the schema-based understanding and practice in cognitive therapy. The clinical benefits from a complementary view of the two approaches will be a wider scope of awareness toward individual...... between fundamental awareness work in gestalt therapy and the tendency within cognitive therapy toward incorporating mindfulness as a therapeutic tool. In the conclusion of the article, additional complementary points between the two approaches are outlined. Keywords: integrative therapy, gestalt...
In vitro evaluation of the effect of botanical formulations used in the control of Aedes aegypti L. (Diptera: Culicidae) on liver enzymes.

Science.gov (United States)

Porto, Karla Rejane de Andrade; Motti, Priscilla Rezende; Machado, Alexandre Alves; Roel, Antonia Railda

2016-01-01

Dengue fever is a viral disease transmitted by the Aedes aegypti Linn. (1792) (Diptera: Culicidae) mosquito, which is endemic in several regions of Brazil. Alternative methods for the control of the vector include botanical insecticides, which offer advantages such as lower environmental contamination levels and less likelihood of resistant populations. Thus, in this study, the ability of botanical insecticide formulations to inhibit the activity of the liver enzymes serum cholinesterase and malate dehydrogenase was evaluated. Inhibition profiles were assessed using in vitro assays for cholinesterase and malate dehydrogenase activity and quantitated by ultraviolet-visible spectroscopy at 410nm to 340nm. Insecticide products formulated from cashew nutshell liquid [A] and ricinoleic acid [B] showed cholinesterase activity levels of 6.26IU/mL and 6.61IU/mL, respectively, while the control level for cholinesterase was 5-12IU/mL. The products did not affect the level of 0.44IU/mL established for malate dehydrogenase, as the levels produced by [A] and [B] were 0.43IU/mL and 0.45IU/mL, respectively. Our findings show that in vitro testing of the formulated products at concentrations lethal to A. aegypti did not affect the activity of cholinesterase and malate dehydrogenase, indicating the safety of these products.
A proteomic view at the biochemistry of syntrophic butyrate oxidation in Syntrophomonas wolfei.

Directory of Open Access Journals (Sweden)

Alexander Schmidt

Full Text Available In syntrophic conversion of butyrate to methane and CO2, butyrate is oxidized to acetate by secondary fermenting bacteria such as Syntrophomonas wolfei in close cooperation with methanogenic partner organisms, e.g., Methanospirillum hungatei. This process involves an energetically unfavourable shift of electrons from the level of butyryl-CoA oxidation to the substantially lower redox potential of proton and/or CO2 reduction, in order to transfer these electrons to the methanogenic partner via hydrogen and/or formate. In the present study, all prominent membrane-bound and soluble proteins expressed in S. wolfei specifically during syntrophic growth with butyrate, in comparison to pure-culture growth with crotonate, were examined by one- and two-dimensional gel electrophoresis, and identified by peptide fingerprinting-mass spectrometry. A membrane-bound, externally oriented, quinone-linked formate dehydrogenase complex was expressed at high level specifically during syntrophic butyrate oxidation, comprising a selenocystein-linked catalytic subunit with a membrane-translocation pathway signal (TAT, a membrane-bound iron-sulfur subunit, and a membrane-bound cytochrome. Soluble hydrogenases were expressed at high levels specifically during growth with crotonate. The results were confirmed by native protein gel electrophoresis, by formate dehydrogenase and hydrogenase-activity staining, and by analysis of formate dehydrogenase and hydrogenase activities in intact cells and cell extracts. Furthermore, constitutive expression of a membrane-bound, internally oriented iron-sulfur oxidoreductase (DUF224 was confirmed, together with expression of soluble electron-transfer flavoproteins (EtfAB and two previously identified butyryl-CoA dehydrogenases. Our findings allow to depict an electron flow scheme for syntrophic butyrate oxidation in S. wolfei. Electrons derived from butyryl-CoA are transferred through a membrane-bound EtfAB:quinone oxidoreductase (DUF
Music Therapy: A Career in Music Therapy

Science.gov (United States)

About Music Therapy & Music Therapy Training M usic therapy is a healthcare profession that uses music to help individuals of all ages improve physical, cognitive, emotional, and social functioning. Music therapists work with children and adults with developmental ...
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.
40 CFR 161.34 - Flagging of studies for potential adverse effects.

Science.gov (United States)

2010-07-01

... a type listed in paragraph (b) of this section to support an application for new or amended... feeding study or combined chronic feeding/oncogenicity study 83-1 Cholinesterase inhibition NOEL less than... ADI 9 Subchronic feeding study 82-1 Cholinesterase inhibition NOEL less than 100 times the current...
Determination of pesticide residues in blood samples of villagers ...

African Journals Online (AJOL)

user

The spray-workers, during the activity of spraying crops, are ... cholinesterase inhibitor, it was recorded as a potent neurotoxic agent ... organic pesticide poisoning, of which around 73% were males and 27% ... analysis of blood will provide evidence of exposure of the body to ...... Occupational illness from cholinesterase ...
Qualitative and quantitative two-dimensional thin-layer chromatography/high performance liquid chromatography/diode-array/electrospray-ionization-time-of-flight mass spectrometry of cholinesterase inhibitors.

Science.gov (United States)

Mroczek, Tomasz

2016-09-10

Recently launched thin-layer chromatography-mass spectrometry (TLC-MS) interface enabling extraction of compounds directly from TLC plates into MS ion source was unusually extended into two-dimensional thin-layer chromatography/high performance liquid chromatography (2D, TLC/HPLC) system by its a direct connection to a rapid resolution 50×2.1mm, I.D. C18 column compartment followed by detection by diode array (DAD) and electrospray ionisation time-of-flight mass spectrometry (ESI-TOF-MS). In this way, even not separated bands of complicated mixtures of natural compounds could be analysed structurally, only within 1-2min after development of TLC plates. In comparison to typically applied TLC-MS interface, no ion suppression for acidic mobile phases was observed. Also, substantial increase in ESI-TOF-MS sensitivities and quality of spectra, were noticed. It has been utilised in combination with TLC- based bioautographic approaches of acetylcholinesterase (AChE) inhibitors, However, it can be also applied in any other procedures related to bioactivity (e.g. 2,2-Diphenyl-1-picryl-hydrazyl-DPPH screen test for radicals). This system has been also used for determination of half maximal inhibitory concentration (IC50 values) of the active inhibitor-galanthamine, as an example. Moreover, AChE inhibitory potencies of some of purified plant extracts, never studied before, have been quantitatively measured. This is first report of usage such the 2D TLC/HPLC/MS system both for qualitative and quantitative evaluation of cholinesterase inhibitors in biological matrices. Copyright © 2016 Elsevier B.V. All rights reserved.
Enhancing attention in neurodegenerative diseases: current therapies and future directions

Directory of Open Access Journals (Sweden)

Sharma Kanchan

2016-01-01

Full Text Available We all experience at least occasional lapses in attention but in some neurological conditions, loss of attention is pervasive and debilitating. Treating deficits in attention first requires an understanding of the neurobiology of attention, which we now understand to be a set of different cognitive processes. Cholinesterase inhibitors are already established as effective attentional enhancers used in the treatment of certain dementias. Other stimulant agents such as modafanil, amphetamine and methylphenidate have demonstrated limited success in healthy individuals where attention is already optimal and clinical trials in patients with neurological disease are sparse. Dietary and lifestyle changes are gaining increasing prominence, as are experimental treatments such as deep brain stimulation and transcranial magnetic stimulation. As the therapeutic arsenal widens, clinicians will be able to match specific treatments to selective deficits in attention, giving patients a tailored management plan. Here we review common diseases that impair attention and emphasise how an understanding of attentional processing within the brain might lead to improved therapeutic strategies.
Is plasma β-glucuronidase a novel human biomarker for monitoring anticholinesterase pesticides exposure? A Malaysian experience

International Nuclear Information System (INIS)

Inayat-Hussain, Salmaan H.; Lubis, Syarif Husin; Sakian, Noor Ibrahim Mohamed; Ghazali, Ahmad Rohi; Ali, Noor Suhailah; El Sersi, Magdi; Toong, Lee Mun; Zainal, Awang Mat; Hashim, Suhaimi; Ghazali, Mohd Shariman; Saidin, Mohd Nazri; Rahman, Ab Razak Ab; Rafaai, Mohd Jamil Mohd; Omar, Sollahudin; Rapiai, Rafiah; Othman, Radziah; Chan, Lee Tiong; Johari, Amran; Soon, Wong Hing; Salleh, Abdul Rahim; Satoh, Tetsuo

2007-01-01

A cross-sectional study was conducted to investigate the effects of acute and chronic pesticide exposure on the plasma β-glucuronidase enzyme activity among five patients of acute pesticide poisoning in Tengku Ampuan Rahimah Hospital, Klang, 230 farmers in the MADA area, Kedah and 49 fishermen in Setiu, Terengganu. The duration of pesticide exposure among the patients was unknown, but the plasma samples from patients were collected on day one in the hospital. The duration of pesticide exposure among the farmers was between 1 and 45 years. The β-glucuronidase activity was compared with plasma cholinesterase activity in the same individual. The plasma cholinesterase activity was measured using Cholinesterase (PTC) Reagent set kit (Teco Diagnostics, UK) based on colorimetric method, while the plasma β-glucuronidase activity was measured fluorometrically based on β-glucuronidase assay. The plasma cholinesterase activity was significantly reduced (p 0.05). The plasma β-glucuronidase activity among the farmers was significantly elevated (p 0.05). The plasma cholinesterase activity was positively correlated with the plasma β-glucuronidase activity among the farmers (r = 0.205, p 0.05). Thus, plasma β-glucuronidase enzyme activity can be measured as a biomarker for the chronic exposure of pesticide. However, further studies need to be performed to confirm whether plasma β-glucuronidase can be a sensitive biomarker for anticholinesterase pesticide poisoning
In vitro evaluation of the effect of botanical formulations used in the control of Aedes aegypti L. (Diptera: Culicidae on liver enzymes.

Directory of Open Access Journals (Sweden)

Karla Rejane de Andrade Porto

Full Text Available Abstract: INTRODUCTION: Dengue fever is a viral disease transmitted by the Aedes aegypti Linn. (1792 (Diptera: Culicidae mosquito, which is endemic in several regions of Brazil. Alternative methods for the control of the vector include botanical insecticides, which offer advantages such as lower environmental contamination levels and less likelihood of resistant populations. Thus, in this study, the ability of botanical insecticide formulations to inhibit the activity of the liver enzymes serum cholinesterase and malate dehydrogenase was evaluated. METHODS: Inhibition profiles were assessed using in vitro assays for cholinesterase and malate dehydrogenase activity and quantitated by ultraviolet-visible spectroscopy at 410nm to 340nm. RESULTS Insecticide products formulated from cashew nutshell liquid [A] and ricinoleic acid [B] showed cholinesterase activity levels of 6.26IU/mL and 6.61IU/mL, respectively, while the control level for cholinesterase was 5-12IU/mL. The products did not affect the level of 0.44IU/mL established for malate dehydrogenase, as the levels produced by [A] and [B] were 0.43IU/mL and 0.45IU/mL, respectively. CONCLUSIONS Our findings show that in vitro testing of the formulated products at concentrations lethal to A. aegypti did not affect the activity of cholinesterase and malate dehydrogenase, indicating the safety of these products.
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

Full Text Available Introduction. On the contrary to the adult population exposed to pesticides, mostly on occupational basis, rural children are mostly exposed to pesticides deposited in the environment. However, even this constant, distributed in time exposure to low concentrations of pesticides may led to permanent health disorders and limit children’s harmonious development. Objective. The main objective of the study was to evaluate the usefulness of aacetylcholinesterase (AChE and butyrylcholinesterase (BuChE activity determination as a marker of children’s environmental exposure to pesticides. An additional aim was to evaluate the usefulness of sweat patches as a novel, non-invasive method of detection of pesticides in sweat as a measure of pesticide exposure. Materials and method. A total of 108 children living in areas of intense pesticide use, and as a control group, 92 children living in an agro-tourist area were enrolled in the study. The AChE and BuChE activity was assayed colorimetricaly in diluted whole blood or plasma, respectively. In addition, selected pesticides were measured by GC/MS analysis in samples of the subject’s sweat absorbed onto a sorbent. Results. The study demonstrated significantly lower AChE and BuChE activity, respectively, in the diluted whole blood and plasma of children exposed to pesticides, compared to the control group (p<0.001 and p=0.003, respectively. The measured mean level of AChE activity was 241.63 ± 26.76 and 348.0±46.95 mU/µmolHb in the exposed and the control group, respectively, whereas the mean activity of BuChE was 424.1±81.1 and 458.6 ± 86.5 mmol/L/min. In addition, pesticide metabolites were detected in 19 (17.6% sweat samples collected from exposed children. Conclusions. 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

Regeneration of Red Cell Cholinesterase Activity Following Pralidoxime (2-PAM) Infusion in First 24 h in Organophosphate Poisoned Patients.

Science.gov (United States)

Goel, Parul; Gupta, Nidhi; Singh, Surjit; Bhalla, Ashish; Sharma, Navneet; Gill, K D

2012-01-01

Oximes such as pralidoxime chloride reactivate acetylcholinesterase. However their role in management of organophosphate poisoning is controversial. The study was carried out to find effectiveness of pralidoxime chloride (2-PAM) in regenerating red cell acetyl cholinesterase in first 24 h following administration of it in dose recommended by WHO. Eight patients with OPP [chlorpyriphos (3), phorate (3), dichlorvos (1) and monocrotophos (1) who fulfilled the criteria for inclusion were investigated. In addition to decontamination and atropine, all these patients were administered 30 mg/kg body wt of 2-PAM as bolus dose followed by 7.5 mg/kg body wt/h with maximum dose being 500 mg/h as continuous infusion till first 24 h. Red cell AChE activity was estimated every 15 min for first 4 h, one hourly for next 4 h and then 2 hourly till 24 h and subsequently without 2-PAM every 12 h till 7 days or discharge or death which ever earlier. In all the patients maximum increase in activity was observed in first 4 h following which rise was very slow despite continued 2-PAM infusion and reaching a steady state in 20 h in all the cases. The increase in red cell AChE activity observed in diethyl group at 24 h of 2-PAM infusion was 154% vs. 81% in dimethyl group. At 7 days the increase in activity was 215% vs. 118% respectively. However on multiple repeated ANOVA, no statistically significant difference was observed between diethyl and dimethyl groups at admission and discharge (P > 0.05). Similarly no significant difference was observed in three groups when patients were categorized according to WHO classification of organophosphates (P > 0.05). The maximum increase in red cell AChE activity occurs in first 4 h of 2-PAM administration followed by a slow increase despite 2-PAM infusion till 24 h.
Muscle-Specific Tyrosine Kinase and Myasthenia Gravis Owing to Other Antibodies.

Science.gov (United States)

Rivner, Michael H; Pasnoor, Mamatha; Dimachkie, Mazen M; Barohn, Richard J; Mei, Lin

2018-05-01

Around 20% of patients with myasthenia gravis are acetylcholine receptor antibody negative; muscle-specific tyrosine kinase antibodies (MuSK) were identified as the cause of myasthenia gravis in 30% to 40% of these cases. Anti MuSK myasthenia gravis is associated with specific clinical phenotypes. One is a bulbar form with fewer ocular symptoms. Others show an isolated head drop or symptoms indistinguishable from acetylcholine receptor-positive myasthenia gravis. These patients usually respond well to immunosuppressive therapy, but not as well to cholinesterase inhibitors. Other antibodies associated with myasthenia gravis, including low-density lipoprotein receptor-related protein 4, are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.
Family Therapy

Science.gov (United States)

Family therapy Overview Family therapy is a type of psychological counseling (psychotherapy) that can help family members improve communication and resolve conflicts. Family therapy is usually provided by a psychologist, ...
Kinetics and molecular docking studies of loganin, morroniside and 7-O-galloyl-D-sedoheptulose derived from Corni fructus as cholinesterase and β-secretase 1 inhibitors.

Science.gov (United States)

Bhakta, Himanshu Kumar; Park, Chan Hum; Yokozawa, Takako; Min, Byung-Sun; Jung, Hyun Ah; Choi, Jae Sue

2016-06-01

We evaluated the major active components isolated from Corni Fructus: loganin, morroniside, and 7-O-galloyl-D-sedoheptulose as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) for use in Alzheimer's disease treatment. These compounds exhibited predominant cholinesterase (ChEs) inhibitory effects with IC50 values of 0.33, 3.95, and 10.50 ± 1.16 µM, respectively, for AChE, and 33.02, 37.78, and 87.94 ± 4.66 µM, respectively, for BChE. Kinetics studies revealed that loganin and 7-O-galloyl-D-sedoheptulose inhibited AChE with characteristics typical of mixed inhibitors, while morroniside was found to be a noncompetitive inhibitor against AChE and also exerted mixed BChE inhibitory activities. For BACE1, loganin showed noncompetitive type inhibitory effects, while morroniside and 7-O-galloyl-D-sedoheptulose were found to be mixed inhibitors. Furthermore, these compounds exhibited dose-dependent inhibitory activity with ONOO(-)-mediated protein tyrosine nitration. Molecular docking simulation of these compounds demonstrated negative binding energies for ChEs, and BACE1, indicating high affinity and tighter binding capacity for the active site of the enzyme. Loganin was the most potent inhibitor against both ChEs and BACE1. The data suggest that these compounds together can act as a triple inhibitor of AChE, BChE, and BACE1, providing a preventive and therapeutic strategy for Alzheimer's disease treatment.
Meaning of dancing therapy in therapy of clients with psychological diseases

OpenAIRE

NĚMCOVÁ, Barbora

2010-01-01

Bachelor thesis deals with meaning and effects of Dance therapy in frame of medical therapy of clients with psychical disease. Theoretical part defines words like dance, movement and Dance therapy. This part also describes history of dance, meaning and aims of Dance therapy, its school, aims and divisions. Mensioned are person of dance therapist, personalities connected with dance and Dance therapy, target groups of clients suitable for Dance therapy, importance of Dance therapy for clients w...
Anticholinesterase effect of eserine (physostigmine in fish and crustacean species

Directory of Open Access Journals (Sweden)

Monserrat José M.

2001-01-01

Full Text Available The kinetic characteristic (Km of cholinesterase from the crab Chasmagnathus granulata, the shrimp Farfantepenaeus paulensis and the fish Odontesthes bonaeriensis were compared and correlated with the anticholinesterasic effect of eserine (physostigmine. For the crustaceans, the estimated Km values were about 5-8 times higher than that estimated for the fish (0.04 mM. In the crab and the shrimp, the concentration of eserine which inhibited 50% of cholinesterase activity (IC50 was estimated as 5.33x10-4 and 4.33x10-4 mM, respectively. In both cases, it was significantly higher (P < 0.05 than that estimated for the fish larvae (7.43x10-5 mM. A high Km could reflect a lower affinity of the cholinesterase for its natural substrate, acetylcholine, or for substrate analogues such as carbamates and organophosphorous pesticides. If we consider the IC50 for eserine as an index of enzyme susceptibility to pesticide inhibition, the cholinesterase from the fish larvae may be a better useful tool in assays for pesticide biomonitoring than that from crustacean species.
Persistent symptoms in agricultural workers exposed to organophosphate pesticides

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Martha E. Palacios N

2011-07-01

Full Text Available Objective: to evaluate the prevalence of these symptoms and their relationship with pesticide exposure and the cholinesterase levels in agricultural workers. Methodology: an analytical cross-sectional study conducted in Mexico. Cholinesterase concentration and symptom frequency were assessed for 106 agricultural workers. Exposure was defined with a composed index of 15 variables. Results: symptom prevalence was 52 out of 100 workers. 31% of workers had 1 to 3 of the symptoms, 16% had 4 to 9 of them and 5% had 10 or more of the symptoms. There was an association, p = 0.03, between days of exposure and persistent symptoms. Likewise, there was an association between exposure level and the presence of probable and specific symptoms. Patients with the highest exposure level had 20% more chances of exhibiting symptoms. Cholinesterase concentration ranges were normal. Anemia was detected in 28% of the population. It was three times as frequent in females as in males (p < 0.001. Conclusions: it was possible to identify the increase of persistent symptoms in workers with cholinesterase levels that are usually considered to be normal.
Behaviour therapy for obesity treatment considering approved drug therapy

Directory of Open Access Journals (Sweden)

Wasem, Jürgen

2008-05-01

Full Text Available Introduction: Obesity is a worldwide health problem whose prevalence is on the increase. Many obesity-associated diseases require intensive medical treatment and are the cause of a large proportion of health-related expenditures in Germany. Treatment of obesity includes nutritional, exercise and behaviour therapy, usually in combination. The goal of behaviour therapy for obesity is to bring about a long-term alteration in the eating and exercise habits of overweight and obese individuals. Under certain circumstances, drug treatment may be indicated. Objectives: What is the effectiveness of behaviour therapy for obesity considering approved drugs reduce weight under medical, economic, ethical-social and legal aspects? Methods: A systematic review was conducted using relevant electronic literature databases. Publications chosen according to predefined criteria are evaluated by approved methodical standards of the evidence-based medicine systematically and qualitatively. Results: In total 18 studies, included one HTA and one meta-analysis could be identified according to the predefined inclusion criteria. Three studies compare behaviour therapy to other therapy forms (advice or instruction on nutritional changes, physical activity or a combination of the two, six studies evaluate different forms of behaviour therapy, four studies and four studies compare behaviour therapies mediated by Internet or telephone. Three studies could be identified examining the effect of the combination of behaviour and drug therapy. Furthermore one HTA and one meta-analysis could be included in the evaluation. The behaviour therapy in comparison with other therapy forms reveals a higher effectiveness. In comparison of the different therapeutic approaches of the behaviour therapy intensive behaviour therapy forms and group therapy show a higher effectiveness. Studies related to behaviour therapy based on media support demonstrate a weight reduction both through the
Sex Therapy

Science.gov (United States)

Sex therapy Overview Sex therapy is a type of psychotherapy — a general term for treating mental health problems by talking with a mental health professional. Through sex therapy, you can address concerns about sexual function, ...
Changes of serum pancreatic stone protein and cholinesterase contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage

Directory of Open Access Journals (Sweden)

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.
Serum Total Cholinesterase Activity on Admission Is Associated with Disease Severity and Outcome in Patients with Traumatic Brain Injury.

Directory of Open Access Journals (Sweden)

Qing-Hong Zhang

Full Text Available Traumatic brain injury (TBI is one of the leading causes of neurological disability. In this retrospective study, serum total cholinesterase (ChE activities were analyzed in 188 patients for diagnostic as well as predictive values for mortality.Within 72 hours after injury, serum ChE activities including both acetylcholinesterase and butyrylcholinesterase were measured. Disease severity was evaluated with Acute Physiology and Chronic Health Evaluation (APACHE II score, Glasgow Coma Score, length of coma, post-traumatic amnesia and injury feature. Neurocognitive and functional scores were assessed using clinical records. Of 188 patients, 146 (77.7% survived and 42 (22.3% died within 90 days. Lower ChE activities were noted in the non-survivors vs. survivors (5.94±2.19 vs. 7.04±2.16 kU/L, p=0.023, in septic vs. non-infected patients (5.93±1.89 vs. 7.31±2.45 kU/L, p=0.0005 and in patients with extremely severe injury vs. mild injury (6.3±1.98 vs. 7.57±2.48 kU/L, p=0.049. The trajectories of serum ChE levels were also different between non-survivors and survivors, septic and non-infected patients, mild and severely injured patients, respectively. Admission ChE activities were closely correlated with blood cell counts, neurocognitive and functional scores both on admission and at discharge. Receiver operating characteristic analysis showed that the area under the curve for ChE was inferior to that for either APACHE II or white blood cell (WBC count. However, at the optimal cutoff value of 5 kU/L, the sensitivity of ChE for correct prediction of 90-day mortality was 65.5% and the specificity was 86.4%. Kaplan-Meier analysis showed that lower ChE activity (5 kU/L (p=0.04. After adjusting for other variables, ChE was identified as a borderline independent predictor for mortality as analyzed by Binary logistic regression (P=0.078.Lowered ChE activity measured on admission appears to be associated with disease severity and outcome for TBI patients.
[The trend of developing new disease-modifying drugs in Alzheimer's disease].

Science.gov (United States)

Arai, Hiroyuki; Furukawa, Katsutoshi; Tomita, Naoki; Ishiki, Aiko; Okamura, Nobuyuki; Kudo, Yukitsuka

2016-03-01

Development of symptomatic treatment of Alzheimer s disease by cholinesterase inhibitors like donepezil was successful. However, it is a disappointment that development of disease-modifying drugs such as anti-amyloid drug based on amyloid-cascade theory has been interrupted or unsuccessful. Therefore, we have to be more cautious regarding inclusion criteria for clinical trials of new drugs. We agree that potentially curative drugs should be started before symptoms begin as a preemptive therapy or prevention trial. The concept of personalized medicine also is important when ApoE4-related amyloid reducing therapy is considered. Unfortunately, Japanese-ADNI has suffered a setback since 2014. However, Ministry of Health, Labour and Welfare gave a final remark that there was nothing wrong in the data managing process in the J-ADNI data center. We should pay more attention to worldwide challenges of speeding up new drug development.
What Is Music Therapy?

Science.gov (United States)

American Music Therapy Association Home Contact News Help/FAQ Members Only Login About Music Therapy & AMTA What is Music Therapy? Definition and ... is Music Therapy? Print Email Share What is Music Therapy What is Music Therapy? Music Therapy is ...
Gestalt therapy and cognitive therapy--contrasts or complementarities?

Science.gov (United States)

Tønnesvang, Jan; Sommer, Ulla; Hammink, James; Sonne, Mikael

2010-12-01

The article investigates the relationship between crucial concepts and understandings in gestalt therapy and cognitive therapy aiming at discussing if and how they can be mutually enriching when considered as complementary parts in a more encompassing integrative therapeutic approach. It is argued that gestalt therapy, defined as a field-theoretical approach to the study of gestalt formation process, can complement the schema-based understanding and practice in cognitive therapy. The clinical benefits from a complementary view of the two approaches will be a wider scope of awareness toward individual and contextual aspects of therapeutic change processes, toward different levels of memory involved in these processes, and toward the relationship between basic needs, sensation and cognition in therapeutic work. Further, a dialogue between the two approaches will pave the way for addressing the connection between fundamental awareness work in gestalt therapy and the tendency within cognitive therapy toward incorporating mindfulness as a therapeutic tool. In the conclusion of the article, additional complementary points between the two approaches are outlined. (PsycINFO Database Record (c) 2010 APA, all rights reserved).
Therapy with radionuclides. Radionuklid-Therapie

Energy Technology Data Exchange (ETDEWEB)

Biersack, H.J.; Hotze, A.L. (Bonn Univ. (Germany). Klinik fuer Nuklearmedizin)

1992-12-01

Radioiodine therapy of benign and malignant thyroid diseases is a well-established procedure in Nuclear Medicine. However, the therapeutic use of radioisotopes in other diseases is relatively unknown among our refering physicians. The therapeutic effects of intraarticular (rheumatoid arthritis) and intracavitary (pleural and peritoneal carcinosis) applications yields good results. The radiophosphorus therapy in polycythemia vera rubra has always to be considered as an alternative to chemotherapy. The use of analgetics may be reduced by pain therapy of bone metastasis by injection of bone-seeking beta emitters like Rh-186 HEDP. Other procedures like therapeutic application of meta-iodo-benzylguanidine in neuroblastoma and malignant pheochromocytoma resulted in at least remissions of the disease. Radioimmunotherapy needs further evaluation before it can be recommended as a routine procedure. (orig.).
Gene Therapy

Science.gov (United States)

Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...
Food therapy and medical diet therapy of Traditional Chinese Medicine

OpenAIRE

Qunli Wu; Xiaochun Liang

2018-01-01

Food therapy of traditional Chinese medicine aims to maintain balanced nutrition through diet. Medical diet therapy, however, is to achieve the balance of Yin and Yang through the combination of nutrition and medicine. Either “food therapy” or “medical diet therapy” aims to keep health, prevent disease, remove illness and slow aging. In recent years, both food therapy and medical diet therapy have been increasingly applied in clinical nutrition therapy. In terms of traditional Chinese food th...
Current perspectives of radiation therapy. History of radiation therapy

International Nuclear Information System (INIS)

Itami, Jun

2011-01-01

More than 100 years have passed since the discovery of X-Strahlen by Roentgen. The history of radiation therapy has evolved under mutual stimulating relationships of the external beam radiation therapy by X-ray tubes and accelerators, and the internal radiation therapy employing radium and other radionuclides. The currently employed technologies in radiation therapy have its origin already till nineteen sixties and the development of physics and engineering have realized the original concept. (author)
Feminist Therapy.

Science.gov (United States)

Laidlaw, Toni; Malmo, Cheryl

1991-01-01

Traces roots of feminist therapy and its independence from traditional and prevalent theories and therapy practices. Asserts that Freudian theory and humanistic assumptions are sexist and contribute to powerlessness of women. In contrast, feminist therapy is seen as dealing directly with client-counselor relationships, trust, advocacy, and…
Emotion Regulation in Schema Therapy and Dialectical Behavior Therapy

NARCIS (Netherlands)

Fassbinder, E.; Schweiger, U.; Martius, D.; Brand-de Wilde, O.; Arntz, A.

2016-01-01

Schema therapy (ST) and dialectical behavior therapy (DBT) have both shown to be effective treatment methods especially for borderline personality disorder. Both, ST and DBT, have their roots in cognitive behavioral therapy and aim at helping patient to deal with emotional dysregulation. However,

Three-dimensional conformal radiation therapy: the tomo-therapy approach

International Nuclear Information System (INIS)

Linthout, N.; Verellen, D.; Coninck, P. de; Bel, A.; Storme, G.

2000-01-01

Conformal radiation therapy allows the possibility of delivering high doses at the tumor volume whilst limiting the dose to the surrounding tissues and diminishing the secondary effects. With the example of the conformal radiation therapy used at the AZ VU8 (3DCRT and tomo-therapy), two treatment plans of a left ethmoid carcinoma will be evaluated and discussed in detail. The treatment of ethmoid cancer is technically difficult for both radiation therapy and surgery because of the anatomic constraints and patterns of local spread. A radiation therapy is scheduled to be delivered after surgical resection of the tumor. The treatment plan for the radiation therapy was calculated on a three-dimensional (3D) treatment planning system based on virtual simulation with a beam's eye view: George Sherouse's Gratis. An effort was made to make the plan as conformal and as homogeneous as possible to deliver a dose of 66 Gy in 33 fractions at the tumor bed with a maximum dose of 56 Gy to the right optic nerve and the chiasma. To establish the clinical utility and potential advantages of tomo-therapy over 3DCRT for ethmoid carcinoma, the treatment of this patient was also planned with Peacock Plant. For both treatment plans the isodose distributions and cumulative dose volume histograms (CDVH) were computed. Superimposing the CDVHs yielded similar curves for the target and an obvious improvement for organs at risk such as the chiasma, brainstem and the left eye when applying tomo-therapy. These results have also been reflected in the tumor control probabilities (equal for both plans) and the normal tissue complication probabilities (NTCP), yielding significant reductions in NTCP for tomo-therapy. The probability of uncomplicated tumor control was 52.7% for tomo-therapy against 38.3% for 3DCRT. (authors)
Medical Art Therapy

Directory of Open Access Journals (Sweden)

Birgul Aydin

2012-03-01

Full Text Available Art therapy is a form of expressive therapy that uses art materials. Art therapy combines traditional psychotherapeutic theories and techniques with an understanding of the psychological aspects of the creative process, especially the affective properties of the different art materials. Medical art therapy has been defined as the clinical application of art expression and imagery with individuals who are physically ill, experiencing physical trauma or undergoing invasive or aggressive medical procedures such as surgery or chemotherapy and is considered as a form of complementary or integrative medicine. Several studies have shown that patients with physical illness benefit from medical art therapy in different aspects. Unlike other therapies, art therapy can take the patients away from their illness for a while by means of creative activities during sessions, can make them forget the illness or lost abilities. Art therapy leads to re-experiencing normality and personal power even with short creative activity sessions. In this article definition, influence and necessity of medical art therapy are briefly reviewed.
NCBI nr-aa BLAST: CBRC-ACAR-01-0762 [SEVENS

Lifescience Database Archive (English)

Full Text Available CBRC-ACAR-01-0762 ref|NP_001070374.1| hypothetical protein LOC534616 [Bos taurus] sp|P32749|CHLE_BOVIN Choli...nesterase precursor (Acylcholine acylhydrolase) (Choline esterase II) (Butyrylcholine esterase) (Pseudocholi...nesterase) gb|AAI23601.1| Similar to Cholinesterase precursor (Acylcholine acylhydrolase) (Choli...ne esterase II) (Butyrylcholine esterase) (Pseudocholinesterase) [Bos taurus] NP_001070374.1 2e-97 40% ...
NCBI nr-aa BLAST: CBRC-XTRO-01-3294 [SEVENS

Lifescience Database Archive (English)

Full Text Available CBRC-XTRO-01-3294 ref|NP_001070374.1| hypothetical protein LOC534616 [Bos taurus] sp|P32749|CHLE_BOVIN Choli...nesterase precursor (Acylcholine acylhydrolase) (Choline esterase II) (Butyrylcholine esterase) (Pseudocholi...nesterase) gb|AAI23601.1| Similar to Cholinesterase precursor (Acylcholine acylhydrolase) (Choli...ne esterase II) (Butyrylcholine esterase) (Pseudocholinesterase) [Bos taurus] NP_001070374.1 1e-135 48% ...
42 CFR 410.35 - X-ray therapy and other radiation therapy services: Scope.

Science.gov (United States)

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false X-ray therapy and other radiation therapy services... Other Health Services § 410.35 X-ray therapy and other radiation therapy services: Scope. Medicare Part B pays for X-ray therapy and other radiation therapy services, including radium therapy and...
Effect of viologen-phosphorus dendrimers on acetylcholinesterase and butyrylcholinesterase activities.

Science.gov (United States)

Ciepluch, Karol; Weber, Monika; Katir, Nadia; Caminade, Anne-Marie; El Kadib, Abdelkrim; Klajnert, Barbara; Majoral, Jean Pierre; Bryszewska, Maria

2013-03-01

The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is the first step in checking whether new compounds can be considered as drugs for treating neurodegenerative diseases. The effect of viologen-phosphorus dendrimers on AChE and BChE activities was studied. The results show that the effects on the cholinesterase activities depend on dendrimer type and size. Viologen dendrimers can interact with the enzymes in two ways: they can bind either to a peripheral site of the enzyme or to amino acids located near the active site, inhibiting catalysis by both cholinesterases. All tested non-toxic viologen-phosphorus dendrimers inhibited the activities of both cholinesterases, showing their potential as new drugs for treating neurodegenerative diseases. Copyright © 2012 Elsevier B.V. All rights reserved.
Personal therapy for undergraduate music therapy students: a survey of AMTA program coordinators.

Science.gov (United States)

Gardstrom, Susan C; Jackson, Nancy A

2011-01-01

The primary purpose of this study was to gather information in order to understand if and how various modalities of personal therapy are employed with undergraduate music therapy students in the United States. AMTA degree program coordinators were asked about 3 therapy modalities, in particular: verbal therapy, music therapy, and expressive arts therapy (excluding music therapy). It was predicted that less than a quarter of the respondents would indicate that personal therapy of any modality was required in their undergraduate curricula, but that a larger percentage would indicate that it was encouraged. Both hypotheses were supported, with just over 14% of the respondents indicating that they require some form of personal therapy and 32% indicating that they encourage it, with 73% of this latter subgroup encouraging verbal therapy and 46% encouraging music therapy. It was further predicted that, when therapy was required or encouraged, it was most often provided by an individual who was associated with the college/university and that therapy was usually provided in a group format. Respondent comments related to these 2 questions revealed considerable confusion between experiential exercises and personal therapy, leading to dubious validity of some of the numerical data. Qualitative treatment of narrative responses illuminated 4 salient issues regarding personal therapy for undergraduate music therapy students, as follows: (a) the legal and ethical feasibility of making personal therapy a requirement; (b) the cost and availability of qualified professionals; (c) the benefits of personal therapy as an integral facet of undergraduate music therapy training and education; and (d) the appropriateness of personal therapy at the undergraduate level of training.
Comparison of dose-volume histograms for Tomo therapy, linear accelerator-based 3D conformal radiation therapy, and intensity-modulated radiation therapy

International Nuclear Information System (INIS)

Ji, Youn-Sang; Dong, Kyung-Rae; Kim, Chang-Bok; Choi, Seong-Kwan; Chung, Woon-Kwan; Lee, Jong-Woong

2011-01-01

Highlights: → Evaluation of DVH from 3D CRT, IMRT and Tomo therapy was conducted for tumor therapy. → The doses of GTV and CTV were compared using DVHs from 3D CRT, IMRT and Tomo therapy. → The GTV was higher when Tomo therapy was used, while the doses of critical organ were low. → They said that Tomo therapy satisfied the goal of radiation therapy more than the others. - Abstract: Evaluation of dose-volume histograms from three-dimensional conformal radiation therapy (3D CRT), intensity-modulated radiation therapy (IMRT), and Tomo therapy was conducted. These three modalities are among the diverse treatment systems available for tumor therapy. Three patients who received tumor therapy for a malignant oligodendroglioma in the cranium, nasopharyngeal carcinoma in the cervical neck, and prostate cancer in the pelvis were selected as study subjects. Therapy plans were made for the three patients before dose-volume histograms were obtained. The doses of the gross tumor volume (GTV) and the clinical target volume (CTV) were compared using the dose-volume histograms obtained from the LINAC-based 3D CRT, IMRT planning station (Varian Eclipse-Varian, version 8.1), and Tomo therapy planning station. In addition, the doses of critical organs in the cranium, cervix, and pelvis that should be protected were compared. The GTV was higher when Tomo therapy was used compared to 3D CRT and the LINAC-based IMRT, while the doses of critical organ tissues that required protection were low. These results demonstrated that Tomo therapy satisfied the ultimate goal of radiation therapy more than the other therapies.
A Play Therapy Approach Focusing on Parent-Child Relationship: Filial Therapy

Directory of Open Access Journals (Sweden)

Banu Tortamis Ozkaya

2015-06-01

Full Text Available Filial therapy is a structured, short-term, and evidence-based play therapy model that aims to train and supervise parents in conducting child-centered play therapy sessions with their children. Filial therapy strengthens the relationship among all family members -in particular the relationship between the parent and the child- and helps parents acquire new and effective parenting skills. Thus parents gain a powerful tool to cope with the difficulties they experience even after therapy sessions end. In this review, filial therapy is explained within the context of its theoretical background and therapy process. Several adaptations of the model and research studies on its effectiveness are also discussed briefly. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(2: 208-220
THE EFFECTIVENESS OF PLAY THERAPY AND MUSICAL THERAPY IN REDUCING THE HOSPITALIZATION STRESS

Directory of Open Access Journals (Sweden)

Yuni Sufyanti Arief

2017-07-01

Full Text Available Introduction: Hospitalization in pediatric patients may caused an anxiety and stress in all age levels. Several techniques can be applied to reduced hospitalization stress in children, such as playing therapy and music therapy. The objective of this study was to analyze the difference of effectiveness between both therapies in reducing the hospitalization stress in 4-6 years old children. Method: A quasy-experimental pre-posttest design was used in this study. There were 18 respondents, divided into three groups, i.e. group one receiving playing therapy, group two receiving music therapy and the last group as control group. Data were collected by using observation sheet before and after intervention to recognize the hospitalization stress. Data were analyzed by using Wilcoxon Signed Rank Test and Mann Whitney U Test with significance level of α<0.05. Result: Result showed that playing therapy and music therapy had significant effect to reduce the hospitalization stress with p=0.027 for play therapy, p=0.024 for musical therapy, and p=0.068 for control. Mann Whitney U Test revealed that there were no difference in the effectiveness of play therapy and musical therapy in reducing the hospitalization stress with p=0.009 for play therapy and control group, p=0.012 for music therapy and control group, and p=0.684 for playing therapy and musical therapy. Discussion: It can be concluded that play therapy and musical therapy are equally effective to reduce the hospitalization stress in children. It’s recommended for nurses in pediatric ward to do playg therapy and musical therapy periodically.
Adaptive therapy.

Science.gov (United States)

Gatenby, Robert A; Silva, Ariosto S; Gillies, Robert J; Frieden, B Roy

2009-06-01

A number of successful systemic therapies are available for treatment of disseminated cancers. However, tumor response is often transient, and therapy frequently fails due to emergence of resistant populations. The latter reflects the temporal and spatial heterogeneity of the tumor microenvironment as well as the evolutionary capacity of cancer phenotypes to adapt to therapeutic perturbations. Although cancers are highly dynamic systems, cancer therapy is typically administered according to a fixed, linear protocol. Here we examine an adaptive therapeutic approach that evolves in response to the temporal and spatial variability of tumor microenvironment and cellular phenotype as well as therapy-induced perturbations. Initial mathematical models find that when resistant phenotypes arise in the untreated tumor, they are typically present in small numbers because they are less fit than the sensitive population. This reflects the "cost" of phenotypic resistance such as additional substrate and energy used to up-regulate xenobiotic metabolism, and therefore not available for proliferation, or the growth inhibitory nature of environments (i.e., ischemia or hypoxia) that confer resistance on phenotypically sensitive cells. Thus, in the Darwinian environment of a cancer, the fitter chemosensitive cells will ordinarily proliferate at the expense of the less fit chemoresistant cells. The models show that, if resistant populations are present before administration of therapy, treatments designed to kill maximum numbers of cancer cells remove this inhibitory effect and actually promote more rapid growth of the resistant populations. We present an alternative approach in which treatment is continuously modulated to achieve a fixed tumor population. The goal of adaptive therapy is to enforce a stable tumor burden by permitting a significant population of chemosensitive cells to survive so that they, in turn, suppress proliferation of the less fit but chemoresistant
Proton therapy

International Nuclear Information System (INIS)

Smith, Alfred R

2006-01-01

Proton therapy has become a subject of considerable interest in the radiation oncology community and it is expected that there will be a substantial growth in proton treatment facilities during the next decade. I was asked to write a historical review of proton therapy based on my personal experiences, which have all occurred in the United States, so therefore I have a somewhat parochial point of view. Space requirements did not permit me to mention all of the existing proton therapy facilities or the names of all of those who have contributed to proton therapy. (review)
Proton-therapy and hadron-therapy ionization chambers

International Nuclear Information System (INIS)

Boissonnat, Guillaume

2015-01-01

In the framework of the ARCHADE project (Advanced Resource Center for Hadron-therapy in Europe), a research project in Carbone ion beam therapy and clinical Proton-therapy, this work investigates the beam monitoring and dosimetry aspects of ion beam therapy. The main goal, here, is to understand the operating mode of air ionization chambers, the detectors used for such applications. This study starts at a very fundamental level as the involved physical and chemical parameters of air were measured in various electric field conditions with dedicated setups and used to produce a simulation tools aiming at reproducing the operating response in high intensity PBS (Pencil Beam Scanning) coming from IBA's (Ion Beam Applications) next generation of proton beam accelerators. In addition, an ionization chamber-based dosimetry equipment was developed, DOSION III, for radiobiology studies conducted at GANIL under the supervision of the CIMAP laboratory. (author)
Radon therapy; Radon in der Therapie

Energy Technology Data Exchange (ETDEWEB)

Spruck, Kaija [Technische Hochschule Mittelhessen, Giessen (Germany). Inst. fuer Medizinische Physik und Strahlenschutz

2017-04-01

Radon therapies are used since more than 100 years in human medicine. Today this method is controversially discussed due to the possible increase of ionizing radiation induced tumor risk. Although the exact mode of biological radiation effect on the cell level is still not known new studies show the efficiency of the radon therapy without side effect for instance for rheumatic/inflammatory or respiratory disorders.
Combined tumor therapy

International Nuclear Information System (INIS)

Wrba, H.

1990-01-01

This comprehensive survey of current methods and achievements first takes a look at the two basic therapies, devoting a chapter each to the surgery and radiotherapy of tumors. The principal subjects of the book, however, are the systemic, adjuvant therapy, biological therapies, hyperthermia and various other therapies (as e.g. treatment with ozone, oxygen, or homeopathic means), and psychotherapy. (MG) With 54 figs., 86 tabs [de
Brain Stimulation Therapies

Science.gov (United States)

... Magnetic Seizure Therapy Deep Brain Stimulation Additional Resources Brain Stimulation Therapies Overview Brain stimulation therapies can play ... for a shorter recovery time than ECT Deep Brain Stimulation Deep brain stimulation (DBS) was first developed ...
The perfect marriage: Solution-focused therapy and motivational interviewing in medical family therapy

Directory of Open Access Journals (Sweden)

Gage Stermensky

2014-01-01

Full Text Available Medical family therapy has many potential uses in behavioral medicine and primary care. Current research was reviewed to determine the most advantageous way to apply solution-focused therapy and motivational interviewing as a perfect marriage in medical family therapy. An extensive literature review was done in the following databases for medical family therapy: Proquest, EBSCO, Medline, and PsychInfo. The search resulted in 86 relevant articles, of which 46 of the most recent were selected for review. Medical family therapy lacks current research that supports solution-focused therapy or motivational interviewing. However, evidence supports the use of solution-focused therapy as a brief format, as well as the closely related intervention, motivational interviewing. While medical family therapy presents many hopeful possibilities in the fields of behavioral medicine, psychology, and marriage and family therapy, little evidence currently exists for the most effective implementation. This review found evidence supporting solution-focused therapy and motivational interviewing as the perfect marriage of the collaborative team approaches for the future implementation and use of specific interventions in medical family therapy.
Music Therapy and Music Therapy Research. Response

DEFF Research Database (Denmark)

Pedersen, Inge Nygaard

2002-01-01

This response to Keynote by Prof. Even Ruud (N)"Music Education and Music Therapy seeks to define these two areas with specific focus on tools and methods for analysis of music as these methods are developed in music therapy. This includes that the music therapist, the music and the client create...
Treatment of Recurrent Chordomas by Percutaneous Ethanol Injection Therapy and Radiation Therapy

International Nuclear Information System (INIS)

Nakajo, M.; Ohkubo, K.; Fukukura, Y.; Nandate, T.; Nakajo, M.

2006-01-01

We report a case of recurrent sacral chordomas that have been successfully controlled by the combination therapy of percutaneous ethanol injection therapy (PEIT) and radiation therapy in a 71-year-old man. PEIT may be one of the adjuvant therapies for recurrent chordomas
Dystonia: Physical Therapy

Science.gov (United States)

... Online Support Frequently Asked Questions Faces of Dystonia Physical Therapy Physical therapy may be an important component of treating ... everyday tasks, Since dystonia is a neurological disorder, physical therapy does not treat the dystonia directly but ...

Physical therapy and occupational therapy in Parkinson's disease

NARCIS (Netherlands)

Radder, D.L.M.; Sturkenboom, I.H.W.M.; Nimwegen, M. van; Keus, S.H.; Bloem, B.R.; Vries, N.M. de

2017-01-01

Current medical management is only partially effective in controlling the symptoms of Parkinson's disease. As part of comprehensive multidisciplinary care, physical therapy and occupational therapy aim to support people with Parkinson's disease in dealing with the consequences of their disease in
CAM therapies among primary care patients using opioid therapy for chronic pain

Directory of Open Access Journals (Sweden)

Mundt Marlon P

2007-05-01

Full Text Available Abstract Background Complementary and alternative medicine (CAM is an increasingly common therapy used to treat chronic pain syndromes. However; there is limited information on the utilization and efficacy of CAM therapy in primary care patients receiving long-term opioid therapy. Method A survey of CAM therapy was conducted with a systematic sample of 908 primary care patients receiving opioids as a primary treatment method for chronic pain. Subjects completed a questionnaire designed to assess utilization, efficacy and costs of CAM therapies in this population. Results Patients were treated for a variety of pain problems including low back pain (38.4%, headaches (9.9%, and knee pain (6.5%; the average duration of pain was 16 years. The median morphine equivalent opioid dose was 41 mg/day, and the mean dose was 92 mg/day. Forty-four percent of the sample reported CAM therapy use in the past 12 months. Therapies utilized included massage therapy (27.3%, n = 248, chiropractic treatment (17.8%, n = 162, acupuncture (7.6%, n = 69, yoga (6.1%, n = 55, herbs and supplements (6.8%, n = 62, and prolotherapy (5.9%, n = 54. CAM utilization was significantly related to age female gender, pain severity income pain diagnosis of neck and upper back pain, and illicit drug use. Medical insurance covered chiropractic treatment (81.8% and prolotherapy (87.7%, whereas patients primarily paid for other CAM therapies. Over half the sample reported that one or more of the CAM therapies were helpful. Conclusion This study suggests CAM therapy is widely used by patients receiving opioids for chronic pain. Whether opioids can be reduced by introducing such therapies remains to be studied.
CAM therapies among primary care patients using opioid therapy for chronic pain.

Science.gov (United States)

Fleming, Sara; Rabago, David P; Mundt, Marlon P; Fleming, Michael F

2007-05-16

Complementary and alternative medicine (CAM) is an increasingly common therapy used to treat chronic pain syndromes. However; there is limited information on the utilization and efficacy of CAM therapy in primary care patients receiving long-term opioid therapy. A survey of CAM therapy was conducted with a systematic sample of 908 primary care patients receiving opioids as a primary treatment method for chronic pain. Subjects completed a questionnaire designed to assess utilization, efficacy and costs of CAM therapies in this population. Patients were treated for a variety of pain problems including low back pain (38.4%), headaches (9.9%), and knee pain (6.5%); the average duration of pain was 16 years. The median morphine equivalent opioid dose was 41 mg/day, and the mean dose was 92 mg/day. Forty-four percent of the sample reported CAM therapy use in the past 12 months. Therapies utilized included massage therapy (27.3%, n = 248), chiropractic treatment (17.8%, n = 162), acupuncture (7.6%, n = 69), yoga (6.1%, n = 55), herbs and supplements (6.8%, n = 62), and prolotherapy (5.9%, n = 54). CAM utilization was significantly related to age female gender, pain severity income pain diagnosis of neck and upper back pain, and illicit drug use. Medical insurance covered chiropractic treatment (81.8%) and prolotherapy (87.7%), whereas patients primarily paid for other CAM therapies. Over half the sample reported that one or more of the CAM therapies were helpful. This study suggests CAM therapy is widely used by patients receiving opioids for chronic pain. Whether opioids can be reduced by introducing such therapies remains to be studied.
[Music therapy and depression].

Science.gov (United States)

Van Assche, E; De Backer, J; Vermote, R

2015-01-01

Music therapy is a predominantly non-verbal psychotherapy based on music improvisation, embedded in a therapeutic relationship. This is the reason why music therapy is also used to treat depression. To examine the efficacy of music therapy and to report on the results of recent research into the value of music therapy as a treatment for depression. We reviewed the literature on recent research into music therapy and depression, reporting on the methods used and the results achieved, and we assessed the current position of music therapy for depression in the context of evidence-based scientific research. A wide variety of research methods was used to investigate the effects of using music therapy as a psychotherapy. Most studies focused usually on the added value that music therapy brings to the standard form of psychiatric treatment, when administered with or without psychopharmacological support. Music therapy produced particularly significant and favourable results when used to treat patients with depression. Current research into music therapy and depression points to a significant and persistent reduction in patients' symptoms and to improvements in their quality of life. However, further research is needed with regard to the best methods of illustrating the effects of music therapy.
Physical Therapy (For Parents)

Science.gov (United States)

... Staying Safe Videos for Educators Search English Español Physical Therapy KidsHealth / For Parents / Physical Therapy Print en español Terapia física Physical Therapy Basics Doctors often recommend physical therapy (PT) ...
Effectiveness of hypnosis therapy and Gestalt therapy as depression treatments

Directory of Open Access Journals (Sweden)

Elizabeth González-Ramírez

2017-03-01

Full Text Available We analyzed the effectiveness of two psychological therapies to treat depression in the Culiacan population, Mexico. According to criteria of MINI (international Neuropsychiatric interview, 30 individuals from a total of 300 were selected and diagnosed with some kind of depression. Patients were divided in three groups: 1 treatment with hypnosis therapy, 2 treatment with Gestalt-hypnosis therapy, and 3 control group. Before and after the treatments the Beck Anxiety Inventory (BAI was applied to know the depression level of the analyzed groups. The results show that the three groups were presenting a moderated level of depression. The groups under hypnosis therapy and Gestalt-hypnosis therapy show statistical differences between pre-test and post-test. The hypnosis therapy shows significant statistic differences to treat depression with respect to the other two groups. In conclusion, the therapeutic hypnosis is an effective treatment and has relevance to treat depression, while other therapeutic treatments tend to be slow and with minor result. This study is the first of this kind carried out in Culiacan in Sinaloa, Mexico.
Use of 2 D-NMR in the structural study of a Trichilia hirta (Meliaceae) isolated limonoid; Utilizacao de RMN-2D na elucidacao estrutural de um limonoide isolado de Trichilia hirta (meliaceae)

Energy Technology Data Exchange (ETDEWEB)

Cortez, Diogenes A.G. [Universidade Estadual de Maringa, PR (Brazil). Dept. de Farmacia-Bioquimica; Vieira, Paulo C; Fernandes, Joao B; Silva, M.Fatima G.F. da; Ferreira, A Gilberto [Sao Carlos Univ., SP (Brazil). Dept. de Quimica

1992-12-31

We have recently studied a T. hirta specie and obtained a limonoid which has a structure similar to the hirtine. The obtained limonoid differs from the hirtine by the absence of an epoxy group in C-14 and C-15, and a propionyl oxy group replacement by a iso butyryl oxy bound to a C-12. NMR-2 D has been used for the structural study of the limonoid obtained from the Trichilia hirta (meliaceae) 8 refs., 1 fig., 3 tabs.
Multipotent MAO and cholinesterase inhibitors for the treatment of Alzheimer's disease: synthesis, pharmacological analysis and molecular modeling of heterocyclic substituted alkyl and cycloalkyl propargyl amine.

Science.gov (United States)

Samadi, Abdelouahid; de los Ríos, Cristóbal; Bolea, Irene; Chioua, Mourad; Iriepa, Isabel; Moraleda, Ignacio; Bartolini, Manuela; Andrisano, Vincenza; Gálvez, Enrique; Valderas, Carolina; Unzeta, Mercedes; Marco-Contelles, José

2012-06-01

The synthesis, pharmacological evaluation and molecular modeling of heterocyclic substituted alkyl and cycloalkyl propargyl amines 1-7 of type I, and 9-12 of type II, designed as multipotent inhibitors able to simultaneously inhibit monoamine oxidases (MAO-A/B) as well as cholinesterase (AChE/BuChE) enzymes, as potential drugs for the treatment of Alzheimer's disease, are described. Indole derivatives 1-7 of type I are well known MAO inhibitors whose capacity to inhibit AChE and BuChE was here investigated for the first time. As a result, compound 7 was identified as a MAO-B inhibitor (IC(50) = 31 ± 2 nM) and a moderately selective eqBuChE inhibitor (IC(50) = 4.7 ± 0.2 μM). Conversely, the new and readily available 5-amino-7-(prop-2-yn-1-yl)-6,7,8,9-tetrahydropyrido[2,3-b][1,6]naphthyridine derivatives 9-13 of type II are poor MAO inhibitors, but showed AChE selective inhibition, compound 12 being the most attractive as it acts as a non-competitive inhibitor on EeAChE (IC(50) = 25 ± 3 nM, K(i) = 65 nM). The ability of this compound to interact with the AChE peripheral binding site was confirmed by kinetic studies and by molecular modeling investigation. Studies on human ChEs confirmed that 12 is a selective AChE inhibitor with inhibitory potency in the submicromolar range. Moreover, in agreement with its mode of action, 12 was shown to be able to inhibit Aβ aggregation induced by hAChE by 30.6%. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

Science.gov (United States)

Halasa, Salaheldin; Dickinson, Eva

2014-02-01

From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.
Effects of selected metal oxide nanoparticles on Artemia salina larvae: evaluation of mortality and behavioural and biochemical responses.

Science.gov (United States)

Gambardella, Chiara; Mesarič, Tina; Milivojević, Tamara; Sepčić, Kristina; Gallus, Lorenzo; Carbone, Serena; Ferrando, Sara; Faimali, Marco

2014-07-01

The aim was to investigate the toxicity of selected metal oxide nanoparticles (MO-NPs) on the brine shrimp Artemia salina, by evaluating mortality and behavioural and biochemical responses. Larvae were exposed to tin(IV) oxide (stannic oxide (SnO2)), cerium(IV) oxide (CeO2) and iron(II, III) oxide (Fe3O4) NPs for 48 h in seawater, with MO-NP suspensions from 0.01 to 1.0 mg/mL. Mortality and behavioural responses (swimming speed alteration) and enzymatic activities of cholinesterase, glutathione-S-transferase and catalase were evaluated. Although the MO-NPs did not induce any mortality of the larvae, they caused changes in behavioural and biochemical responses. Swimming speed significantly decreased in larvae exposed to CeO2 NPs. Cholinesterase and glutathione-S-transferase activities were significantly inhibited in larvae exposed to SnO2 NPs, whereas cholinesterase activity significantly increased after CeO2 NP and Fe3O4 NP exposure. Catalase activity significantly increased in larvae exposed to Fe3O4 NPs. In conclusion, swimming alteration and cholinesterase activity represent valid endpoints for MO-NP exposure, while glutathione-S-transferase and catalase activities appear to be NP-specific.
Alternative Therapy of Animals – Homeopathy and Other Alternative Methods of Therapy

Directory of Open Access Journals (Sweden)

Løken Torleiv

2002-03-01

Full Text Available Alternative therapy of animals is described, in the meaning of alternatives to veterinary therapy traditionally accepted by veterinary faculties and schools and included in their curricula. Alternative therapy composes of different disciplines, of which homeopathy is emphasised in this presentation. Information is given on the use and interest of such therapy among veterinarians and animal owners. Homeopathy as other alternative therapies, may offer great advances, if they induce any effect. Some of the disciplines are based on a scientifically accepted documentation. Others, and homeopathy in particular, are missing such a documentation of effect. The justification of including alternative therapy in treating animals is discussed. Research in alternative therapy of animals is greatly needed, in particular to evaluate therapeutic methods which are in extensive use without any documented effect. An ongoing research project in Norway on the effect of homeopathic treatment of mastitis in cows is shortly presented.
Monitoring acetylcholinesterase levels in migrant agricultural workers and their children using a portable test kit.

Science.gov (United States)

Higgins, G M; Muñiz, J F; McCauley, L A

2001-02-01

The EQM Research, Inc., portable test kit was evaluated as a surveillance tool for blood cholinesterase levels among migrant workers and their children. Laboratory validation demonstrated a linear relationship between the reference Ellman and kit methods (Ellman = 0.95 x kit result + 0.82, r2 = 0.98). Pre- and post-season cholinesterase levels measured in 70 farm workers were within normal ranges, but significantly different at 28.5 and 29.7 U/g Hb, respectively (paired t-test, p = 0.014). Results from 98 migrant farm worker children and a comparison group of 53 age-matched non-agricultural children showed that cholinesterase levels were not significantly different between the agricultural and non-agricultural children (ANOVA, p = 0.69). These data demonstrate that a portable test kit can provide useful data pesticide exposures when measurements are made in a temperature-controlled setting.
Chemotherapy and molecular target therapy combined with radiation therapy

International Nuclear Information System (INIS)

Akimoto, Tetsuo

2012-01-01

Combined chemotherapy and radiation therapy has been established as standard treatment approach for locally advanced head and neck cancer, esophageal cancer and so on through randomized clinical trials. However, radiation-related morbidity such as acute toxicity also increased as treatment intensity has increased. In underlining mechanism for enhancement of normal tissue reaction in chemo-radiation therapy, chemotherapy enhanced radiosensitivity of normal tissues in addition to cancer cells. Molecular target-based drugs combined with radiation therapy have been expected as promising approach that makes it possible to achieve cancer-specific enhancement of radiosensitivity, and clinical trials using combined modalities have been performed to evaluate the feasibility and efficacy of this approach. In order to obtain maximum radiotherapeutic gain, a detailed understanding of the mechanism underlying the interaction between radiation and Molecular target-based drugs is indispensable. Among molecular target-based drugs, inhibitors targeting epidermal growth factor receptor (EGFR) and its signal transduction pathways have been vigorously investigated, and mechanisms regarding the radiosensitizing effect have been getting clear. In addition, the results of randomized clinical trials demonstrated that radiation therapy combined with cetuximab resulted in improvement of overall and disease-specific survival rate compared with radiation therapy in locally advanced head and neck cancer. In this review, clinical usefulness of chemo-radiation therapy and potential molecular targets for potentiation of radiation-induced cell killing are summarized. (author)
Music therapy in kindergarten

OpenAIRE

Šírová, Michaela

2017-01-01

This work deals with the subject of music therapy in a special kindergarten for the children with combined disabilities. In the theoretical part it clarifies the concept and principle of music therapy and characterizes the types of disabilities that occur at researched clients. As a research method were used observation and interviews with three music therapists from the institution. KEYWORDS Music therapy, preschool education, special pedagogy, group music therapy,individual music therapy, p...
Art therapy, psychodrama, and verbal therapy. An integrative model of group therapy in the treatment of adolescents with anorexia nervosa and bulimia nervosa.

Science.gov (United States)

Diamond-Raab, Lisa; Orrell-Valente, Joan K

2002-04-01

Anorexia nervosa and bulimia nervosa typically afflict individuals in adolescence. Given the intractability of these diseases in combination with the natural recalcitrance of adolescence, treatment with this population presents a daunting challenge. Traditional group therapy that focuses on verbal therapy is often not effective with this population, particularly in the acute stages of the diseases. A group therapy approach that integrates art therapy, psychodrama, and verbal therapy offers an innovative alternative to traditional group therapy.
Complementary and Integrative Therapies

Science.gov (United States)

... include: • Acupressure and acupuncture • Aromatherapy • Art therapy and music therapy • Chiropractic medicine and massage • Guided imagery • Meditation and ... should I avoid? • Is this complementary therapy (name therapy) safe? Is there research showing it is safe? • Are there side effects ...
Differentiated NSC-34 cells as an in vitro Cell Model for VX

Science.gov (United States)

2014-09-11

principally as potent cholinesterase inhibitors . The toxicity of these compounds and their mode of action are attributed to the inhibition of the enzyme...necrosis, with more cells undergoing apoptosis. Acetylcholinesterase inhibition by VX Since VX is an AChE inhibitor , the amount of VX-induced AChE...acetyl- cholinesterase by in vitro methods. Acta Medica (Hradec Kralove) 48:81–6. Landshamer S, Hoehn M, Barth N, et al. (2008). Bid-induced release of
Interpersonal, cognitive analytic and other integrative therapies versus other psychological therapies for depression

OpenAIRE

Hunot, Vivien; Moore, Theresa HM; Caldwell, Deborah; Davies, Philippa; Jones, Hannah; Lewis, Glyn; Churchill, Rachel

2010-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: To examine the effectiveness and acceptability of all integrative therapies compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of different integrative therapy models (IPT, CAT, psychodynamic-interpersonal therapy, CBASP, counselling) compared with all other psychological therapy approaches for acute depression.To examine the e...
Drug Therapy.

Science.gov (United States)

He, Ri-Hui; Tao, Ran

2017-01-01

This chapter first summarizes the therapy of addiction disorder, and elaborates on the progress of medication. First, the difference between dependency and addiction are introduced. The basic principles of the therapy of substance and non-substance addiction are then put forward. It is also pointed out in this chapter that with the progress of the study, the goal of addiction disorder therapy is expected to transfer from reducing the relapse and harm of the addiction to completely eliminating and recovering from it. This chapter also introduces the progress of psychological addiction elimination technology, especially the "Unconditioned Stimulus Retrieval Extinction Paradigm and Conditioned Stimulus Retrieval Extinction Paradigm" and PITDH technology. Finally it is pointed out that in addiction disorder therapy, comprehensive intervention has become a trend. With regard to the medication for addiction disorders, this chapter also includes the progress and deficiencies of substance and non-substance addiction. In terms of addiction disorder rehabilitation, the foundation of substance addiction is medication which is, however, limited for non-substance addiction. The key to the rehabilitation of addiction disorder is psycho-behavioral therapy, which is especially effective in eliminating craving.
External radiation therapy of prostatic carcinoma and its relationship to hormonal therapy

International Nuclear Information System (INIS)

Takada, Chitose; Ito, Koushiro; Nishi, Junko; Yamamoto, Toshihiro; Hatanaka, Yoshimi; Baba, Yuji; Takahashi, Mutsumasa.

1995-01-01

From 1980 to 1990, a total of 54 patients with prostatic carcinoma were treated with external radiation therapy at the Kumamoto National Hospital. Ten patients were classified as Stage B, 22 as Stage C, and another 22 as Stage D according to the American Urological Association Clinical Staging System. The 5-year survival for all 54 patients was 30%. The 5-year disease-specific survival was 67% for Stage B, 47% for Stage C, and 26% for Stage D. The 5-year survival was 43% for patients in whom radiation therapy was initiated immediately after the first diagnosis or with less than one year of hormonal therapy, while it was 0% for patients in whom radiation therapy was initiated after more than one year of hormonal therapy (p=0.01). The cause of intercurrent death was acute myocardial infarction in four patients and acute cardiac failure in one. Four of these patients received hormonal therapy for more than one year. The incidence of radiation-induced proctitis was not severe. This study suggests that long-term hormonal therapy prior to radiation therapy worsens the prognosis of patients with prostatic carcinoma. (author)

Predictors of trimodality therapy and trends in therapy for malignant pleural mesothelioma.

Science.gov (United States)

Nelson, David B; Rice, David C; Niu, Jiangong; Atay, Scott M; Vaporciyan, Ara A; Antonoff, Mara B; Hofstetter, Wayne L; Walsh, Garrett L; Swisher, Stephen G; Roth, Jack A; Tsao, Anne S; Gomez, Daniel R; Giordano, Sharon H; Mehran, Reza J; Sepesi, Boris

2018-05-01

Malignant pleural mesothelioma is an aggressive and rare malignancy that frequently recurs despite aggressive therapy. We evaluated the frequency of treatment with surgery, radiation or chemotherapy, changes in therapy and survival over time and factors associated with the receipt of trimodality therapy. The National Cancer Database (NCDB) was used to query patients with histologically proven malignant pleural mesothelioma (2004-14). Treatment over time was evaluated using the Armitage trend test. Factors associated with the receipt of trimodality therapy were analysed using logistic regression. Among 20 561 patients, only 4028 (20%) underwent cancer-directed surgery; 533 (2.6%) of whom received trimodality therapy. From 2004 to 2014, the use of surgery with chemotherapy increased 87% (P 26 miles for treatment were more likely to undergo trimodality therapy. Additional factors associated with the receipt of trimodality therapy include age less than 70, Charlson comorbidity score of 0 and presence of private insurance. Many malignant pleural mesothelioma patients are not treated with trimodality therapy, with significant variation in treatment patterns. Referrals to high-volume and specialized centres may help offer more therapeutic options and trial or registry enrolment.
Treatment of Alzheimer's disease in Brazil: I. Cognitive disorders

Directory of Open Access Journals (Sweden)

Francisco de Assis Carvalho do Vale

Full Text Available Abstract This article reports the recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology for the treatment of Alzheimer's disease (AD in Brazil, with special focus on cognitive disorders. It constitutes a revision and broadening of the 2005 guidelines based on a consensus involving researchers (physicians and non-physicians in the field. The authors carried out a search of articles published since 2005 on the MEDLINE, LILACS and Cochrane Library databases. The search criteria were pharmacological and non-pharmacological treatment of cognitive disorders in AD. Studies retrieved were categorized into four classes, and evidence into four levels, based on the 2008 recommendations of the American Academy of Neurology. The recommendations on therapy are pertinent to the dementia phase of AD. Recommendations are proposed for the treatment of cognitive disorders encompassing both pharmacological (including acetyl-cholinesterase inhibitors, memantine and other drugs and substances and non-pharmacological (including cognitive rehabilitation, physical activity, occupational therapy, and music therapy approaches. Recommendations for the treatment of behavioral and psychological symptoms of dementia due to Alzheimer's disease are included in a separate article of this edition.
Rumination-focused cognitive behaviour therapy vs. cognitive behaviour therapy for depression

DEFF Research Database (Denmark)

Hvenegaard, Morten; Watkins, Ed R; Poulsen, Stig

2015-01-01

BACKGROUND: Cognitive behavioural therapy is an effective treatment for depression. However, one third of the patients do not respond satisfactorily, and relapse rates of around 30 % within the first post-treatment year were reported in a recent meta-analysis. In total, 30-50 % of remitted patients...... of future depression. Rumination-focused cognitive behavioural therapy is a psychotherapeutic treatment targeting rumination. Because rumination plays a major role in the initiation and maintenance of depression, targeting rumination with rumination-focused cognitive behavioural therapy may be more...... effective in treating depression and reducing relapse than standard cognitive behavioural therapy. METHOD/DESIGN: This study is a two-arm pragmatic randomised controlled superiority trial comparing the effectiveness of group-based rumination-focused cognitive behaviour therapy with the effectiveness...
Radiotechnologies and gene therapy

International Nuclear Information System (INIS)

Xia Jinsong

2001-01-01

Gene therapy is an exciting frontier in medicine today. Radiologist will make an uniquely contribution to these exciting new technologies at every level by choosing sites for targeting therapy, perfecting and establishing routes of delivery, developing imaging strategies to monitor therapy and assess gene expression, developing radiotherapeutic used of gene therapy
[Physical therapy for scars].

Science.gov (United States)

Masanovic, Marguerite Guillot

2013-01-01

Physical therapy consists notably of hand or mechanical massages, pressure therapy using various fabrics or splints, cryotherapy, laser therapy, etc. It forms part of the range of therapies used to treat pathological scars, including medical and surgical treatment. While the results are often satisfactory for hypertrophic scars, they remain uncertain for major keloids.
Dance movement therapy in the concept of expressive arts-therapy

OpenAIRE

Martinec, Renata

2013-01-01

Dance Movement Therapy is a complementary method which includes using and analyzing of different aspects of body-experience and body-expression such us movement, mimics, pantomime, touch… In Dance Movement Therapy body is dominant media of therapeutic process. So this kind of therapy may have positive influence on physiological awareness, body expression of emotions, inducing unconscious impulses, and improving new strategies of behaviour through exploring new patterns and qualities of mov...
Radionuclide therapy of endocrine-related cancer; Nuklearmedizinische Therapie endokriner Tumoren

Energy Technology Data Exchange (ETDEWEB)

Kratochwil, C.; Giesel, F.L. [Universitaetsklinikum Heidelberg, Abteilung Nuklearmedizin, Heidelberg (Germany)

2014-10-15

This article gives an overview of the established radionuclide therapies for endocrine-related cancer that already have market authorization or are currently under evaluation in clinical trials. Radioiodine therapy is still the gold standard for differentiated iodine-avid thyroid cancer. In patients with bone and lung metastases (near) total remission is seen in approximately 50 % and the 15-year survival rate for these patients is approximately 90 %. In contrast to the USA, meta-iodobenzylguanidine (MIBG) therapy has market approval in Europe. According to the current literature, in the setting of advanced stage neuroblastoma and malignant pheochromocytoma or paraganglioma, radiological remission can be achieved in > 30 % and symptom control in almost 80 % of the treated patients. Somatostatin receptor targeted radionuclide therapies (e.g. with DOTATATE or DOTATOC) demonstrated promising results in phase 2 trials, reporting progression-free survival in the range of 24-36 months. A first phase 3 pivotal trial for intestinal carcinoids is currently recruiting and another trial for pancreatic neuroendocrine tumors is planned. Radiopharmaceuticals based on glucagon-like peptide 1 (GLP1) or minigastrins are in the early evaluation stage for application in the treatment of insulinomas and medullary thyroid cancer. In general, radiopharmaceutical therapy belongs to the group of so-called theranostics which means that therapy is tailored for individual patients based on molecular imaging diagnostics to stratify target positive or target negative tumor phenotypes. (orig.) [German] Dieser Artikel gibt einen Ueberblick ueber die etablierten sowie weitere vielversprechende, aktuell im Rahmen von Studien eingesetzte nuklearmedizinische Therapiemoeglichkeiten diverser endokrinologischer Neoplasien. Die Radiojodtherapie ist unveraendert die Therapie der Wahl beim differenzierten, jodspeichernden Schilddruesenkarzinom. Im metastasierten Stadium sind in ca. 50 % der Faelle noch
Play therapy in perspective theory of eco systemic therapy

Directory of Open Access Journals (Sweden)

Sofwan Adiputra

2017-11-01

Full Text Available Play therapy is a counseling approach for children applying toys, games, and other play media to communicate to the children "language." One of the Play therapy models that combine ecosystems as being formed by an inseparable reciprocal relationship between living things, and their environment is Eco systemic Play Therapy (EPT. Ecosystem Play Therapy as a hybrid model that integrates the concepts of science biology, several models of child psychotherapy, and developmental theories. This model is not eclectic. Rather, it is the integration of several models to create an independent model that is different from the sum of its parts. The focus of EPT is on the process of optimizing the implementation of the child's function as the context of the child's ecosystem or world. EPT is developed from a phenomenological philosophical perspective, in contrast to traditional perspectives.
Traditional Chinese medicines and Alzheimer’s disease

Directory of Open Access Journals (Sweden)

Tzong-Yuan Wu

2011-06-01

Full Text Available Traditional Chinese medicines have been widely investigated for the treatment of Alzheimer’s disease (AD because none of the current therapies—either the cholinesterase inhibitors or antagonist of N-methyl-d-aspartate receptors—has profound effects on halting the progression of AD. In recent years, scientists have isolated many active compounds from herbs, which can alleviate dementia and neurodegenerative syndrome with fewer side effects than conventional drugs and, thus, are regarded as promising drug candidates for AD therapy. In this review, we summarize the latest research progress on six herbs for AD therapy—Huperzia serrata, Amaryllidaceae family, Ginkgo biloba, Uncaria rhynchophylla, Polygala tenuifolia, and Salvia officinalis—and focus on the analysis of their active components and possible mechanisms of pharmacological actions on AD.
Music Therapy for Seniors

OpenAIRE

SLUNEČKOVÁ, Petra

2014-01-01

This bachelor thesis deals with the use of music therapy in the lives of seniors. The target of this thesis is to map the possibilities of using music therapy ways with seniors and to recommend a suitable music therapy resources on the basis of the research and evaluation of obtained dates. The theoretical part describes the term "the music therapy", e.g. concept, definition, types and forms, the development of music therapy, the history, methods and techniques. This age group is defined in t...
Patient predictors of response to cognitive behaviour therapy and schema therapy for depression.

Science.gov (United States)

Carter, Janet D; McIntosh, Virginia Vw; Jordan, Jennifer; Porter, Richard J; Douglas, Katie; Frampton, Christopher M; Joyce, Peter R

2018-01-01

Few studies have examined differential predictors of response to psychotherapy for depression. Greater understanding about the factors associated with therapeutic response may better enable therapists to optimise response by targeting therapy for the individual. The aim of the current exploratory study was to examine patient characteristics associated with response to cognitive behaviour therapy and schema therapy for depression. Participants were 100 outpatients in a clinical trial randomised to either cognitive behaviour therapy or schema therapy. Potential predictors of response examined included demographic, clinical, functioning, cognitive, personality and neuropsychological variables. Individuals with chronic depression and increased levels of pre-treatment negative automatic thoughts had a poorer response to both cognitive behaviour therapy and schema therapy. A treatment type interaction was found for verbal learning and memory. Lower levels of verbal learning and memory impairment markedly impacted on response to schema therapy. This was not the case for cognitive behaviour therapy, which was more impacted if verbal learning and memory was in the moderate range. Study findings are consistent with the Capitalisation Model suggesting that therapy that focuses on the person's strengths is more likely to contribute to a better outcome. Limitations were that participants were outpatients in a randomised controlled trial and may not be representative of other depressed samples. Examination of a variety of potential predictors was exploratory and requires replication.
Massage therapy and exercise therapy in patients with multiple sclerosis: a randomized controlled pilot study.

Science.gov (United States)

Negahban, Hossein; Rezaie, Solmaz; Goharpey, Shahin

2013-12-01

The primary aim was to investigate the comparative effects of massage therapy and exercise therapy on patients with multiple sclerosis. The secondary aim was to investigate whether combination of both massage and exercise has an additive effect. Randomized controlled pilot trial with repeated measurements and blinded assessments. Local Multiple Sclerosis Society. A total of 48 patients with multiple sclerosis were randomly assigned to four equal subgroups labelled as massage therapy, exercise therapy, combined massage-exercise therapy and control group. The treatment group received 15 sessions of supervised intervention for five weeks. The massage therapy group received a standard Swedish massage. The exercise therapy group was given a combined set of strength, stretch, endurance and balance exercises. Patients in the massage-exercise therapy received a combined set of massage and exercise treatments. Patients in the control group were asked to continue their standard medical care. Pain, fatigue, spasticity, balance, gait and quality of life were assessed before and after intervention. Massage therapy resulted in significantly larger improvement in pain reduction (mean change 2.75 points, P = 0.001), dynamic balance (mean change, 3.69 seconds, P = 0.009) and walking speed (mean change, 7.84 seconds, P = 0.007) than exercise therapy. Patients involved in the combined massage-exercise therapy showed significantly larger improvement in pain reduction than those in the exercise therapy (mean change, 1.67 points, P = 0.001). Massage therapy could be more effective than exercise therapy. Moreover, the combination of massage and exercise therapy may be a little more effective than exercise therapy alone.
Intra-articular therapies for osteoarthritis.

Science.gov (United States)

Yu, Shirley P; Hunter, David J

2016-10-01

Conventional medical therapies for osteoarthritis are mainly palliative in nature, aiming to control pain and symptoms. Traditional intra-articular therapies are not recommended in guidelines as first line therapy, but are potential alternatives, when conventional therapies have failed. Current and future intra-articular drug therapies for osteoarthritis are highlighted, including corticosteroids, hyaluronate, and more controversial treatments marketed commercially, namely platelet rich plasma and mesenchymal cell therapy. Intraarticular disease modifying osteoarthritis drugs are the future of osteoarthritis treatments, aiming at structural modification and altering the disease progression. Interleukin-1β inhibitor, bone morphogenic protein-7, fibroblast growth factor 18, bradykinin B2 receptor antagonist, human serum albumin, and gene therapy are discussed in this review. The evolution of drug development in osteoarthritis is limited by the ability to demonstrate effect. High quality trials are required to justify the use of existing intra-articular therapies and to advocate for newer, promising therapies. Challenges in osteoarthritis therapy research are fundamentally related to the complexity of the pathological mechanisms of osteoarthritis. Novel drugs offer hope in a disease with limited medical therapy options. Whether these future intra-articular therapies will provide clinically meaningful benefits, remains unknown.
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.
CAM therapies among primary care patients using opioid therapy for chronic pain

OpenAIRE

Fleming, Sara; Rabago, David P; Mundt, Marlon P; Fleming, Michael F

2007-01-01

Abstract Background Complementary and alternative medicine (CAM) is an increasingly common therapy used to treat chronic pain syndromes. However; there is limited information on the utilization and efficacy of CAM therapy in primary care patients receiving long-term opioid therapy. Method A survey of CAM therapy was conducted with a systematic sample of 908 primary care patients receiving opioids as a primary treatment method for chronic pain. Subjects completed a questionnaire designed to as...
Inhalation Therapy in Horses.

Science.gov (United States)

Cha, Mandy L; Costa, Lais R R

2017-04-01

This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobials. Copyright © 2016 Elsevier Inc. All rights reserved.
42 CFR 418.74 - Waiver of requirement-Physical therapy, occupational therapy, speech-language pathology, and...

Science.gov (United States)

2010-10-01

..., occupational therapy, speech-language pathology, and dietary counseling. 418.74 Section 418.74 Public Health... requirement—Physical therapy, occupational therapy, speech-language pathology, and dietary counseling. (a) A... providing physical therapy, occupational therapy, speech-language pathology, and dietary counseling services...
42 CFR 418.72 - Condition of participation: Physical therapy, occupational therapy, and speech-language pathology.

Science.gov (United States)

2010-10-01

..., occupational therapy, and speech-language pathology. 418.72 Section 418.72 Public Health CENTERS FOR MEDICARE... therapy, occupational therapy, and speech-language pathology. Physical therapy services, occupational therapy services, and speech-language pathology services must be available, and when provided, offered in...
Music therapy CD creation for initial pediatric radiation therapy: a mixed methods analysis.

Science.gov (United States)

Barry, Philippa; O'Callaghan, Clare; Wheeler, Greg; Grocke, Denise

2010-01-01

A mixed methods research design was used to investigate the effects of a music therapy CD (MTCD) creation intervention on pediatric oncology patients' distress and coping during their first radiation therapy treatment. The music therapy method involved children creating a music CD using interactive computer-based music software, which was "remixed" by the music therapist-researcher to extend the musical material. Eleven pediatric radiation therapy outpatients aged 6 to 13 years were randomly assigned to either an experimental group, in which they could create a music CD prior to their initial treatment to listen to during radiation therapy, or to a standard care group. Quantitative and qualitative analyses generated multiple perceptions from the pediatric patients, parents, radiation therapy staff, and music therapist-researcher. Ratings of distress during initial radiation therapy treatment were low for all children. The comparison between the two groups found that 67% of the children in the standard care group used social withdrawal as a coping strategy, compared to 0% of the children in the music therapy group; this trend approached significance (p = 0.076). MTCD creation was a fun, engaging, and developmentally appropriate intervention for pediatric patients, which offered a positive experience and aided their use of effective coping strategies to meet the demands of their initial radiation therapy treatment.
42 CFR 409.23 - Physical therapy, occupational therapy and speech-language pathology.

Science.gov (United States)

2010-10-01

...-language pathology. 409.23 Section 409.23 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... § 409.23 Physical therapy, occupational therapy and speech-language pathology. Medicare pays for... therapy or speech-language pathology services must be furnished— (1) By qualified physical therapists...

Hendee's radiation therapy physics

CERN Document Server

Pawlicki, Todd; Starkschall, George

2016-01-01

The publication of this fourth edition, more than ten years on from the publication of Radiation Therapy Physics third edition, provides a comprehensive and valuable update to the educational offerings in this field. Led by a new team of highly esteemed authors, building on Dr Hendee’s tradition, Hendee’s Radiation Therapy Physics offers a succinctly written, fully modernised update. Radiation physics has undergone many changes in the past ten years: intensity-modulated radiation therapy (IMRT) has become a routine method of radiation treatment delivery, digital imaging has replaced film-screen imaging for localization and verification, image-guided radiation therapy (IGRT) is frequently used, in many centers proton therapy has become a viable mode of radiation therapy, new approaches have been introduced to radiation therapy quality assurance and safety that focus more on process analysis rather than specific performance testing, and the explosion in patient-and machine-related data has necessitated an ...
Play Therapy

Science.gov (United States)

Lawver, Timothy; Blankenship, Kelly

2008-01-01

Play therapy is a treatment modality in which the therapist engages in play with the child. Its use has been documented in a variety of settings and with a variety of diagnoses. Treating within the context of play brings the therapist and the therapy to the level of the child. By way of an introduction to this approach, a case is presented of a six-year-old boy with oppositional defiant disorder. The presentation focuses on the events and interactions of a typical session with an established patient. The primary issues of the session are aggression, self worth, and self efficacy. These themes manifest themselves through the content of the child’s play and narration of his actions. The therapist then reflects these back to the child while gently encouraging the child toward more positive play. Though the example is one of nondirective play therapy, a wide range of variation exists under the heading of play therapy. PMID:19724720
Music therapy improvisation

Directory of Open Access Journals (Sweden)

Mira Kuzma

2001-09-01

Full Text Available In this article, the technique of music therapy – music therapy improvisation is introduced. In this form of music therapy the improvising partners share meaning through the improvisation: the improvisation is not an end in itself: it portrays meaning that is personal, complex and can be shared with the partner. The therapeutic work, then, is meeting and matching the client's music in order to give the client an experience of "being known", being responded through sounds and being able to express things and communicate meaningfully. Rather than the client playing music, the therapy is about developing the engagement through sustained, joint improvisations. In music therapy, music and emotion share fundamental features: one may represent the other, i.e., we hear the music not as music but as dynamic emotional states. The concept of dynamic structure explains why music makes therapeutic sense.
Proton therapy physics

CERN Document Server

2012-01-01

Proton Therapy Physics goes beyond current books on proton therapy to provide an in-depth overview of the physics aspects of this radiation therapy modality, eliminating the need to dig through information scattered in the medical physics literature. After tracing the history of proton therapy, the book summarizes the atomic and nuclear physics background necessary for understanding proton interactions with tissue. It describes the physics of proton accelerators, the parameters of clinical proton beams, and the mechanisms to generate a conformal dose distribution in a patient. The text then covers detector systems and measuring techniques for reference dosimetry, outlines basic quality assurance and commissioning guidelines, and gives examples of Monte Carlo simulations in proton therapy. The book moves on to discussions of treatment planning for single- and multiple-field uniform doses, dose calculation concepts and algorithms, and precision and uncertainties for nonmoving and moving targets. It also exami...
Consumption trends for specific drugs used to treat dementia in the region of Madrid (Spain) from 2002 to 2012.

Science.gov (United States)

de Hoyos-Alonso, M C; Tapias-Merino, E; Meseguer Barros, C M; Sánchez-Martínez, M; Otero, A

2015-09-01

Analysing drug consumption in large population groups lets us observe consumption trends and compare them between different settings. to analyse the time trends for consumption and costs of specific drugs used to treat dementia in the region of Madrid (Spain) and compare trends by sex and age cohort. Descriptive study of cholinesterase inhibitors (N06DA) and memantine (N06DX01) dispensed in Madrid between 2002 and 2012 and covered by the Spain's national health system. Consumption was calculated by analysing changes in DDD (defined daily doses) to find total and yearly increases. The cost was estimated based on DDD price. To compare consumption rates by age and sex, we calculated DDD per 100 inhabitants/day. Between 2002 and 2012, consumption of drugs used to treat dementia increased sixfold. During this period, cholinesterase inhibitors accounted for 76.70% of the drugs consumed and memantine, 23.30%. The estimated cost rose by a by a factor of 5.7 over 11 years (or by a factor of 4 taking into account the use of generic drugs). In 2012, 2.42% of the patients aged 65 or over consumed cholinesterase inhibitors (women 2.82%, men 1.83%) and 0.90% consumed memantine (women 1.10%, men 0.61%). Consumption increased in age cohorts up to 86 to 90 (5.84% for cholinesterase inhibitors and 2.33% for memantine) and declined thereafter. Consumption of cholinesterase inhibitors and memantine gradually increased, but consumption in 2012 did not reach levels equivalent to dementia prevalence figures. Pharmaceutical expenditure restraint measures may temporarily slow the cost increase temporarily but if the same trend of consumption persists, costs will rise. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.
[Play therapy in hospital].

Science.gov (United States)

Gold, Katharina; Grothues, Dirk; Leitzmann, Michael; Gruber, Hans; Melter, Michael

2012-01-01

The following article presents an overview of current research studies on play therapy in the hospital. It highlights individual diagnoses for which play therapy has shown reasonable success. The aim of this review is to describe the current status of the scientific debate on play therapy for sick children in order to allow conclusions regarding the indications for which play therapy is or might be useful.
The effect of Gestalt therapy and cognitive- behavioral therapy on assertiveness in male guidance students

Directory of Open Access Journals (Sweden)

Kh. Aryan

2013-01-01

Full Text Available This study was conducted to investigate the effectiveness of gestalt therapy and cognitive -behavioral therapy on assertiveness in middle school students. This study was a pre-post test experimental design. By cluster sampling between schools in Sharyar two schools were selected randomly. After conducting Gambrel and Rigy Questionnaire, 30 students were selected and assigned to three groups randomly. 8 sessions of gestalt therapy were implemented for one group and 8 sessions of cognitive- behavioral therapy were implemented for another group. The control group received no intervention. ANCOVA and Post hoc LSD Test were applied to analyze data. ANCOVA showed significant differences between groups. Post hoc LSD Test showed significant difference between the control group and the gestalt therapy and between the control group and cognitive -behavioral therapy group(P≤0/01, but there was no significant difference between the gestalt therapy and the cognitive- behavioral therapy group. Both gestalt therapy and cognitive- behavioral therapy had increased the assertiveness.
Laser therapy for cancer

Science.gov (United States)

... this page: //medlineplus.gov/ency/patientinstructions/000905.htm Laser therapy for cancer To use the sharing features ... Lasers are also used on the skin. How Laser Therapy is Used Laser therapy can be used ...
The feminist/emotionally focused therapy practice model: an integrated approach for couple therapy.

Science.gov (United States)

Vatcher, C A; Bogo, M

2001-01-01

Emotionally focused therapy (EFT) is a well-developed, empirically tested practice model for couple therapy that integrates systems, experiential, and attachment theories. Feminist family therapy theory has provided a critique of biased assumptions about gender at play in traditional family therapy practice and the historical absence of discussions of power in family therapy theory. This article presents an integrated feminist/EFT practice model for use in couple therapy, using a case from practice to illustrate key concepts. Broadly, the integrated model addresses gender roles and individual emotional experience using a systemic framework for understanding couple interaction. The model provides practitioners with a sophisticated, comprehensive, and relevant practice approach for working with the issues and challenges emerging for contemporary heterosexual couples.
Radiation therapy for prostate cancer

International Nuclear Information System (INIS)

Nakamura, Katsumasa

2001-01-01

In Japan, where the mortality rate of prostate cancer is lower than in Western countries, radical prostatectomy or hormonal therapy has been applied more frequently than radiation therapy. However, the number of patients with prostate cancer has been increasing recently and the importance of radiation therapy has rapidly been recognized. Although there have been no randomized trials, results from several institutions in Western countries suggest that similar results of cancer control are achieved with either radiation therapy or radical prostatectomy. For higher-risk cases, conformal high-dose therapy or adjuvant hormonal therapy is more appropriate. In this article, the results of radiation therapy for prostate cancer were reviewed, with a view to the appropriate choice of therapy in Japan. (author)
[Therapy of intermediate uveitis].

Science.gov (United States)

Doycheva, D; Deuter, C; Zierhut, M

2014-12-01

Intermediate uveitis is a form of intraocular inflammation in which the vitreous body is the major site of inflammation. Intermediate uveitis is primarily treated medicinally and systemic corticosteroids are the mainstay of therapy. When recurrence of uveitis or side effects occur during corticosteroid therapy an immunosuppressive treatment is required. Cyclosporine A is the only immunosuppressive agent that is approved for therapy of uveitis in Germany; however, other immunosuppressive drugs have also been shown to be effective and well-tolerated in patients with intermediate uveitis. In severe therapy-refractory cases when conventional immunosuppressive therapy has failed, biologics can be used. In patients with unilateral uveitis or when the systemic therapy is contraindicated because of side effects, an intravitreal steroid treatment can be carried out. In certain cases a vitrectomy may be used.
Resistance to Inhibitors of Cholinesterase 3 (Ric-3 Expression Promotes Selective Protein Associations with the Human α7-Nicotinic Acetylcholine Receptor Interactome.

Directory of Open Access Journals (Sweden)

Matthew J Mulcahy

Full Text Available The α7-nicotinic acetylcholine receptor (α7-nAChR is a ligand-gated ion channel widely expressed in vertebrates and is associated with numerous physiological functions. As transmembrane ion channels, α7-nAChRs need to be expressed on the surface of the plasma membrane to function. The receptor has been reported to associate with proteins involved with receptor biogenesis, modulation of receptor properties, as well as intracellular signaling cascades and some of these associated proteins may affect surface expression of α7-nAChRs. The putative chaperone resistance to inhibitors of cholinesterase 3 (Ric-3 has been reported to interact with, and enhance the surface expression of, α7-nAChRs. In this study, we identified proteins that associate with α7-nAChRs when Ric-3 is expressed. Using α-bungarotoxin (α-bgtx, we isolated and compared α7-nAChR-associated proteins from two stably transfected, human tumor-derived cell lines: SH-EP1-hα7 expressing human α7-nAChRs and the same cell line further transfected to express Ric-3, SH-EP1-hα7-Ric-3. Mass spectrometric analysis of peptides identified thirty-nine proteins that are associated with α7-nAChRs only when Ric-3 was expressed. Significantly, and consistent with reports of Ric-3 function in the literature, several of the identified proteins are involved in biological processes that may affect nAChR surface expression such as post-translational processing of proteins, protein trafficking, and protein transport. Additionally, proteins affecting the cell cycle, the cytoskeleton, stress responses, as well as cyclic AMP- and inositol triphosphate-dependent signaling cascades were identified. These results illuminate how α-bgtx may be used to isolate and identify α7-nAChRs as well as how the expression of chaperones such as Ric-3 can influence proteins associating with α7-nAChRs. These associating proteins may alter activities of α7-nAChRs to expand their functionally-relevant repertoire as
Therapy of the burnout syndrome [Therapie des Burnout-Syndroms

Directory of Open Access Journals (Sweden)

Korczak, Dieter

2012-06-01

Full Text Available [english] The prevalence, diagnostics and therapy of the burnout syndrome are increasingly discussed in the public. The unclear definition and diagnics of the burnout syndrome are scientifically criticized. There are several therapies with unclear evidence for the treatment of burnout in existence.The health technology assessment (HTA report deals with the question of usage and efficacy of different burnout therapies.For the years 2006 to 2011, a systematic literature research was done in 31 electronic databases (e.g. EMBASE, MEDLINE, PsycINFO. Important inclusion criteria are burnout, therapeutic intervention and treatment outcome.17 studies meet the inclusion criteria and are regarded for the HTA report. The studies are very heterogeneous (sample size, type of intervention, measuring method, level of evidence. Due to their study design (e.g. four reviews, eight randomized controlled trials the studies have a comparable high evidence: three times 1A, five times 1B, one time 2A, two times 2B and six times 4. 13 of the 17 studies are dealing with the efficacy of psychotherapy and psychosocial interventions for the reduction of burnout (partly in combination with other techniques. Cognitive behaviour therapy leads to the improvement of emotional exhaustion in the majority of the studies. The evidence is inconsistent for the efficacy of stress management and music therapy. Two studies regarding the efficacy of Qigong therapy do not deliver a distinct result. One study proves the efficacy of roots of Rhodiola rosea (evidence level 1B. Physical therapy is only in one study separately examined and does not show a better result than standard therapy.Despite the number of studies with high evidence the results for the efficacy of burnout therapies are preliminary and do have only limited reach. The authors of the studies complain about the low number of skilled studies for the therapy of burnout. Furthermore, they point to the insufficient evaluation of
Depressão vascular no idoso: resposta ao tratamento antidepressivo associado a inibidor das colinesterases Vascular depression in elderly: response to treatment with antidepressant associated to cholinesterase inhibitor

Directory of Open Access Journals (Sweden)

Ricardo Barcelos

2007-01-01

Full Text Available CONTEXTO: Entre os transtornos neuropsiquiátricos ocasionados por eventos cerebrovasculares, a depressão vascular é pouco diagnosticada por médicos não especialistas, causando aumento da morbimortalidade de pacientes idosos. CASO CLÍNICO: Trata-se de um paciente com 67 anos que apresentou resposta parcial a tratamento com inibidores da recaptura de serotonina e efeitos adversos autonômicos graves com outros antidepressivos. A adição de rivastigmina ao citalopram promoveu sucesso terapêutico, com redução de 23 para 7 pontos, na escala de Hamilton para depressão. DISCUSSÃO: O resultado obtido traz novas perspectivas para o tratamento da depressão vascular, sendo necessários ensaios clínicos controlados que evidenciem o benefício da adição dos inibidores das colinesterases aos antidepressivos no tratamento destes pacientes.CONTEXT: Among neuropsychiatric disorders caused by cerebrovascular factors, vascular depression is diagnosed in a small degree by general practitioners, causing morbid-mortality increase in elderly. CASE REPORT: That is a case of a 67 year-old-man with partial response after treatment with a Selective Serotonin Receptors Inhibitor, and severe autonomic adverse effects with other antidepressants. The addition of rivastigmine to citalopram resulted in a therapeutic success, with a reduction of 23 to 7 points on the Hamilton Depressive Scale (HAM-D. DISCUSSION: The result obtained brings new perspectives to the treatment of vascular depression, providing that randomized controlled trials with larger sample sizes confirm the positive effect of the addition of a cholinesterase inhibitor to antidepressants in the treatment of these patients.
Comparison of steroid pulse therapy and conventional oral steroid therapy as initial treatment for autoimmune pancreatitis

International Nuclear Information System (INIS)

Tomiyama, Takashi; Uchida, Kazushige; Matsushita, Mitsunobu; Ikeura, Tsukasa; Fukui, Toshiro; Takaoka, Makoto; Nishio, Akiyoshi; Okazaki, Kazuichi

2011-01-01

The efficacy of oral steroid therapy for autoimmune pancreatitis (AIP) is well known, and oral prednisolone treatment is most usually commenced at 30-40 mg/day, but there have been few reports about comparative studies of oral steroid therapy and steroid pulse therapy as the initial treatment for AIP. We studied the clinical course and image findings to estimate the utility of steroid pulse therapy for AIP, comparing it with oral steroid therapy. Laboratory and image findings were assessed retrospectively in 11 patients who received steroid pulse therapy, and the findings were compared to those in 10 patients who received conventional oral steroid therapy. Change in pancreatic size showed no significant difference between the therapies after 2 weeks of treatment. Significant improvement of lower bile duct strictures after 2 weeks of treatment and that of immunoglobulin values within 6 months were shown with both therapies. However, steroid pulse therapy showed significant improvement of γ-guanosine triphosphate (GTP) in 2 weeks and of alanine aminotransferase (ALT) in 2 and 8 weeks, compared with oral steroid therapy. Moreover, there was one patient in whom the lower bile duct stricture was not improved by oral steroid therapy, but it did show improvement with steroid pulse therapy. Initial steroid pulse therapy is a beneficial alternative to oral steroid therapy for the improvement of bile duct lesions. In future, the accumulation of a larger number of patients receiving steroid pulse therapy is needed, and prospective studies will be required. (author)
[Health differences between male and female migrant agricultural workers in Sinaloa, Mexico].

Science.gov (United States)

Palacios-Nava, Martha Edilia; Moreno-Tetlacuilo, Luz María Angela

2004-01-01

To assess the differences in the prevalence of muscarinic and nicotinic type symptoms and the level of erythrocytic cholinesterase, prior to pesticide exposure, in male and female migrant agricultural workers. A cross-sectional study was carried out in 2001 in Sinaloa State, Mexico, among 488 migrant workers. A questionnaire was applied and erythrocytic cholinesterase levels were measured before the beginning of the agricultural season. The differences by sex were compared using the "t" test for continuous variables and chi2 test for categorical variables. Prevalence odds ratios were also estimated. Statistical significance was assessed using p-values migration type, place of origin, education, and migration time (p=0.000). Women were six times more likely to have anemia and asthma, twice more likely to have parasites and respiratory and gastrointestinal diseases and 38% more likely to suffer from heart disease. They were also at greater prevalence in thirteen of nineteen investigated symptoms. The average cholinesterase level was within normal limits (4.22 U/ml+/-0.77) and it was similar to the levels reported using the Magnotti method. The prevalence of symptoms, illnesses and cholinesterase levels found in this study may serve as baseline values for future comparisons of the health effects of pesticide exposure. The English version of this paper is available at: http://www.insp.mx/salud/index.html.
American Music Therapy Association

Science.gov (United States)

American Music Therapy Association Home Contact News Help/FAQ Members Only Login Quick Links Facts About Music Therapy Qualifications ... with AMTA Sponsor AMTA Events Social Networking Support Music Therapy When you shop at AmazonSmile, Amazon will ...
Population Health and Occupational Therapy.

Science.gov (United States)

Braveman, Brent

2016-01-01

Occupational therapy practitioners play an important role in improving the health of populations through the development of occupational therapy interventions at the population level and through advocacy to address occupational participation and the multiple determinants of health. This article defines and explores population health as a concept and describes the appropriateness of occupational therapy practice in population health. Support of population health practice as evidenced in the official documents of the American Occupational Therapy Association and the relevance of population health for occupational therapy as a profession are reviewed. Recommendations and directions for the future are included related to celebration of the achievements of occupational therapy practitioners in the area of population health, changes to the Occupational Therapy Practice Framework and educational accreditation standards, and the importance of supporting, recognizing, rewarding, and valuing occupational therapy practitioners who assume roles in which direct care is not their primary function. Copyright © 2016 by the American Occupational Therapy Association, Inc.
History of gene therapy.

Science.gov (United States)

Wirth, Thomas; Parker, Nigel; Ylä-Herttuala, Seppo

2013-08-10

Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the concern that has persisted in society. Despite the setbacks gene therapy has faced, success stories have increasingly emerged. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, our knowledge continues to grow and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors which are now producing clinical results. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and address some concerns that have been connected with gene therapy as an important therapeutic modality. Copyright © 2013 Elsevier B.V. All rights reserved.
Combining Voice Therapy and Physical Therapy: A Novel Approach to Treating Muscle Tension Dysphonia

Science.gov (United States)

Craig, Jennifer; Tomlinson, Carey; Stevens, Kristin; Kotagal, Kiran; Fornadley, Judith; Jacobson, Barbara; Garrett, C. Gaelyn; Francis, David O.

2015-01-01

Objective This study investigated the role of a specialized physical therapy program for muscle tension dysphonia patients as an adjunct to standard of care voice therapy. Study Design Retrospective Cohort Study Methods Adult MTD patients seen between 2007 and 2012 were identified from the clinical database. They were prescribed voice therapy and, if concomitant neck pain, adjunctive physical therapy. In a pragmatic observational cohort design, patients underwent one of four potential treatment approaches: voice therapy alone (VT), voice therapy and physical therapy (VT+PT), physical therapy alone (PT), or incomplete/no treatment. Voice handicap outcomes were compared between treatment approaches. Results Of 153 patients meeting criteria (Median age 48 years, 68% female, and 30% had fibromyalgia, chronic pain, chronic fatigue, depression, and/or anxiety), there was a similar distribution of patients with moderate or severe pre-treatment VHI scores across treatment groups (VT 45.5%, VT+PT 43.8%, PT 50%, no treatment 59.1%; p=0.45). Patients treated with VT alone had significantly greater median improvement in VHI than those not treated: 10-point vs. 2-point (p=0.02). Interestingly, median VHI improvement in patients with baseline moderate-severe VHI scores was no different between VT (10), VT+PT (8) and PT alone (10; p=0.99). Conclusions Findings show voice therapy to be an effective approach to treating MTD. Importantly, other treatment modalities incorporating physical therapy had a similar, albeit not significant, improvement in VHI. This preliminary study suggests that physical therapy techniques may have a role in the treatment of a subset of MTD patients. Larger, comparative studies are needed to better characterize the role of physical therapy in this population. PMID:26012419

Aphasia therapy in the age of globalization: cross-linguistic therapy effects in bilingual aphasia.

Science.gov (United States)

Ansaldo, Ana Inés; Saidi, Ladan Ghazi

2014-01-01

Globalization imposes challenges to the field of behavioural neurology, among which is an increase in the prevalence of bilingual aphasia. Thus, aphasiologists have increasingly focused on bilingual aphasia therapy and, more recently, on the identification of the most efficient procedures for triggering language recovery in bilinguals with aphasia. Therapy in both languages is often not available, and, thus, researchers have focused on the transfer of therapy effects from the treated language to the untreated one. This paper discusses the literature on bilingual aphasia therapy, with a focus on cross-linguistic therapy effects from the language in which therapy is provided to the untreated language. Fifteen articles including two systematic reviews, providing details on pre- and posttherapy in the adult bilingual population with poststroke aphasia and anomia are discussed with regard to variables that can influence the presence or absence of cross-linguistic transfer of therapy effects. . The potential for CLT of therapy effects from the treated to the untreated language depends on the word type, the degree of structural overlap between languages, the type of therapy approach, the pre- and postmorbid language proficiency profiles, and the status of the cognitive control circuit.
Multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer’s disease: design, synthesis, biochemical evaluation, ADMET, molecular modeling, and QSAR analysis of novel donepezil-pyridyl hybrids

Directory of Open Access Journals (Sweden)

Bautista-Aguilera OM

2014-10-01

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

CERN Document Server

Eary, Janet F

2013-01-01

One in three of the 30 million Americans who are hospitalized are diagnosed or treated with nuclear medicine techniques. This text provides a succinct overview and detailed set of procedures and considerations for patient therapy with unsealed radioactivity sources. Serving as a complete literature reference for therapy with radiopharmaceuticals currently utilized in practice, this source covers the role of the physician in radionuclide therapy, and essential procedures and protocols required by health care personnel.
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.
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.

Science.gov (United States)

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.
Synthesis of certain new lupinine esters on the base of dialkythiophosphoric and dialkyldithiophosphoric acids and their alkylated iodides

International Nuclear Information System (INIS)

Abduvakhabov, A.A.; Dalimov, D.N.; Aslanov, Kh.A.; Sadykov, A.S.

1976-01-01

Dialkoxyphosphinylthiolupinanes (I), their alkylated iodides (II), and dialkoxythiophosphinylthiolupinanes (III) were synthesized and their anti-cholinesterase activity was studied. The methods of synthesizing the compounds and their physico-chemical constants are given. Compounds I and II were made by reacting bromolupinane with the corresponding potassium o,o-dialkylthiophosphates, obtained from dialkylphosphates, sulfur, and potassium carbonate. The action of iodoalkyls on dialkoxyphosphinylthiolupinanes gave the corresponding iodoalkylates. The compounds obtained are strong inhibitors of cholinesterase and are of interest as insecticides and acaricides
Morality in group and family therapies: multiperson therapies and the 1992 ethics code.

Science.gov (United States)

Lakin, M

1994-11-01

Although virtually every psychotherapeutic approach or orientation has adapted group and family therapy to its conceptions of psychological dysfunctions and how to treat them, levels of training of practitioners in all of these approaches are often insufficient to meet the requirements of ethically as well as technically responsible conduct of treatment for persons in groups and families. The new ethics code (American Psychological Association [APA], 1992) does include a few issues specific to multiperson therapies, but other issues critical to the competent practice of group and family therapy remain unaddressed. The result can be confusing to those applying standards for individual therapy to multiperson therapies. It is argued that the classical ethical concerns of psychotherapists, informed consent, confidentiality, countertransference reactions, aand intrusions of therapist values, require special sensitivity to how they are expressed in mulitperson therapies. Practitioners of group and family therapies must be better sensitized to the technical distinctions and the associated ethical vulnerabilities of the modalities they use. Future planning for revision of the APA ethics code should take these factors into account.
Music therapy

DEFF Research Database (Denmark)

Ridder, Hanne Mette Ochsner

alternate with clear and lucid mental states. These states are important as it is here that it is possible to meet the person’s psychosocial needs. Ketil Normann’s conceps of periods of lucidity are presented and connected to clinical music therapy practice and how it is possible to use music in order...... as a consequence of person-centred care. Umeå University Medical Dissertations. New Series. Ridder, H.M. (2005). Music therapy as a way to enhance lucidity in persons with dementia in advanced stages. In: Esch, A.; Frohne-Hagemann, I.; Laqua, M.; Schirmer, H.; Seitz, E. (Eds.) Jahrbuch Musicktherapie. Forschung...... und Entwicklung Music Therapy Annual. Research and Development. 2005 (1), pp. 25-40. Reichert Verlag Wiesbaden....
Journal of Proton Therapy

Directory of Open Access Journals (Sweden)

Editorial Office

2015-01-01

Full Text Available Journal of Proton Therapy (JPT is an international open access, peer-reviewed journal, which publishes original research, technical reports, reviews, case reports, editorials, and other materials on proton therapy with focus on radiation oncology, medical physics, medical dosimetry, and radiation therapy.No article processing/submission feeNo publication feePeer-review completion within 3-6 weeksImmediate publication after the completion of final author proofreadDOI assignment for each published articleFree access to published articles for all readers without any access barriers or subscriptionThe views and opinions expressed in articles are those of the author/s and do not necessarily reflect the policies of the Journal of Proton Therapy.Authors are encouraged to submit articles for publication in the inaugural issue of the Journal of Proton Therapy by online or email to editor@protonjournal.comOfficial Website of Journal of Proton Therapy: http://www.protonjournal.org/
Mammary carcinoma diagnostics and therapy; Diagnostik und Therapie des Mammakarzinoms

Energy Technology Data Exchange (ETDEWEB)

Fischer, Uwe; Baum, Friedemann (eds.) [Diagnostisches Brustzentrum Goettingen BZG, Goettingen(Germany)

2014-11-01

The book on mammary carcinoma diagnostics and therapy covers the following issues: development, anatomy and physiology of the mammary glands, pathology of benign and malign mammary gland changes, non-imaging diagnostics; mammography; ultrasonic mammography; magnetic resonance tomography of the mammary glands; imaging diagnostics findings; mammary interventions; examination concepts; operative therapy of the mammary carcinoma; chemotherapy of the mammary carcinoma; radio-oncological therapy of the mammary carcinoma; logistics in a medical center for mammary gland diseases; logistics in an interdisciplinary center for mammary diseases; dialogue conduction and psycho-social attendance.
Physical Therapy and Manual Physical Therapy: Differences in Patient Characteristics.

NARCIS (Netherlands)

van Ravensberg, C. D. Dorine; Oostendorp, Rob A B; van Berkel, Lonneke M.; Scholten-Peeters, Gwendolijne G M; Pool, Jan J.M.; Swinkels, Raymond A. H. M.; Huijbregts, Peter A.

2005-01-01

This study compared socio-demographic characteristics, health problem characteristics, and primary process data between database samples of patients referred to physical therapy (PT) versus a sample of patients referred to manual physical therapy (MPT) in the Netherlands. Statistical analysis
Physical therapy and manual physical therapy: Differences in patient characteristics

NARCIS (Netherlands)

van Ravensberg, C. D. Dorine; Oostendorp, R.A.B.; van Berkel, Lonneke M.; Scholten-Peeters, G.G.M.; Pool, J.J.M.; Swinkels, Raymond A. H. M.; Huijbregts, Peter A.

2005-01-01

This study compared socio-demographic characteristics, health problem characteristics, and primary process data between database samples of patients referred to physical therapy (PT) versus a sample of patients referred to manual physical therapy (MPT) in the Netherlands. Statistical analysis
Physical Therapy and Manual Physical Therapy: Differences in Patient Characteristics

NARCIS (Netherlands)

van Ravensberg, C. D. Dorine; Oostendorp, Rob A B; van Berkel, Lonneke M.; Scholten-Peeters, Gwendolijne G. M.; Pool, Jan J.M.; Swinkels, Raymond A. H. M.; Huijbregts, Peter A.

2005-01-01

This study compared socio-demographic characteristics, health problem characteristics, and primary process data between database samples of patients referred to physical therapy (PT) versus a sample of patients referred to manual physical therapy (MPT) in the Netherlands. Statistical analysis
The Use of Dialectical Behavior Therapy (DBT) in Music Therapy: A Sequential Explanatory Study.

Science.gov (United States)

Chwalek, Carolyn M; McKinney, Cathy H

2015-01-01

There are published examples of how dialectical behavior therapy (DBT) and music therapy are effectively being used as separate therapies in the treatment of individuals with a variety of mental health disorders. However, research examining DBT-informed music therapy is limited. The purpose of this study was to determine whether music therapists working in mental health settings are implementing components of DBT in their work, and if so, how and why; and if not, why not and what is their level of interest in such work. We used a sequential explanatory mixed-methods research design implemented in two phases. Phase 1 was a quantitative survey of board-certified music therapists (n=260). Due to a low survey response rate (18%), and to enhance the validity of the findings, Phase 2, an embedded qualitative procedure in the form of interviews with clinicians experienced in the DBT approach, was added to the study. Both survey and interviews inquired about DBT training, use of DBT-informed music therapy, music therapy experiences used to address DBT skills, and experiences of implementing DBT-informed music therapy. Respondents indicating they implement DBT-informed music therapy (38.3%) are using components and adaptations of the standard DBT protocol. Advantages of implementing DBT-informed music therapy were identified, and more than half of the respondents who do not implement DBT in their music therapy practice also perceived this work as at least somewhat important. Disadvantages were also identified and support the need for further research. Components of DBT are used in music therapy and are valued, but there is a lack of empirical evidence to inform, refine, and guide practice. © the American Music Therapy Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Cost-utility analysis of antithyroid drug therapy versus 131I therapy for Graves' disease

International Nuclear Information System (INIS)

Hayashi, Katsumi; Abe, Katsumi; Sakata, Ikuko; Sakaguchi, Chiharu; Yamamoto, Kentaro; Kosuda, Shigeru

2005-01-01

There is no comparative cost-utility study between 131 I therapy and antithyroid drugs (ATD) therapy for Graves' disease, though 131 I therapy has higher remission rate and less side effects. The objective of the study was to analyze the cost-utility of ATD therapy versus 131 I therapy by calculating life-long medical costs and utility, based on the responses of Graves' disease patients to questionnaires. To determine the expected cost and expected utility, a decision tree analysis was designed on the basis of the 2 competing strategies of ATD therapy versus 131 I therapy. A simulation of 1,000 female patients weighing≥50 kg who assumed to experience the onset of Graves' disease at the age of 30, to first complain of thyrotoxic symptoms and moderate goiter 2-3 mo. previously, and to undergo a 40-years-long cohort study, was created for each strategy using a decision tree and baselines of other relevant variables. The variables and costs were based on the literature and hospital bills. The maximum and minimum values of utility were defined as 1.0 and 0.0, respectively. Future costs and utilities were discounted 5%. The medical costs and utilities were 85,739-88,650 yen/patient/40 years and 16.47-16.56/patient/40 years, respectively, for the ATD therapy strategy, and 81,842 yen/patient/40 years and 17.41/patient/40 years, respectively, for the 131 I therapy strategy. These results quantitatively demonstrated that the 131 I therapy strategy was superior to the ATD therapy strategy in terms of both cost and utility. 131 I therapy should be used more widely in Japan because of its greater utility and lower cost. (author)
42 CFR 440.110 - Physical therapy, occupational therapy, and services for individuals with speech, hearing, and...

Science.gov (United States)

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Physical therapy, occupational therapy, and..., occupational therapy, and services for individuals with speech, hearing, and language disorders. (a) Physical...) Where applicable, licensed by the State. (b) Occupational therapy. (1) Occupational therapy means...
Amino derivatives of glycyrrhetinic acid as potential inhibitors of cholinesterases.

Science.gov (United States)

Schwarz, Stefan; Lucas, Susana Dias; Sommerwerk, Sven; Csuk, René

2014-07-01

The development of remedies against the Alzheimer's disease (AD) is one of the biggest challenges in medicinal chemistry nowadays. Although not completely understood, there are several strategies fighting this disease or at least bringing some relief. During the progress of AD, the level of acetylcholine (ACh) decreases; hence, a therapy using inhibitors should be of some benefit to the patients. Drugs presently used for the treatment of AD inhibit the two ACh controlling enzymes, acetylcholinesterase as well as butyrylcholinesterase; hence, the design of selective inhibitors is called for. Glycyrrhetinic acid seems to be an interesting starting point for the development of selective inhibitors. Although its glycon, glycyrrhetinic acid is known for being an AChE activator, several derivatives, altered in position C-3 and C-30, exhibited remarkable inhibition constants in micro-molar range. Furthermore, five representative compounds were subjected to three more enzyme assays (on carbonic anhydrase II, papain and the lipase from Candida antarctica) to gain information about the selectivity of the compounds in comparison to other enzymes. In addition, photometric sulforhodamine B assays using murine embryonic fibroblasts (NiH 3T3) were performed to study the cytotoxicity of these compounds. Two derivatives, bearing either a 1,3-diaminopropyl or a 1H-benzotriazolyl residue, showed a BChE selective inhibition in the single-digit micro-molar range without being cytotoxic up to 30μM. In silico molecular docking studies on the active sites of AChE and BChE were performed to gain a molecular insight into the mode of action of these compounds and to explain the pronounced selectivity for BChE. Copyright © 2014 Elsevier Ltd. All rights reserved.
Comparison of Efficacy of Neural Therapy and Physical Therapy in Chronic Low Back Pain

OpenAIRE

Atalay, Nilgun Simsir; Sahin, Fusun; Atalay, Ali; Akkaya, Nuray

2013-01-01

The aim of this prospective study was to evaluate the effects of neural therapy, and physical therapy on level of pain, disability, quality of life, and psychological status in patients with chronic low back pain. Patients admitted to the physical therapy and rehabilitation outpatient clinic with the complaint of low back pain of at least 3 months duration. Group 1 (n=27), physical therapy (PT, hotpack, ultrasound, TENS 15 sessions), group 2 (n=33), neural therapy (NT, 1:1 mixture of 20 mg/mL...
The synergistic effect of nanoparticles in photodynamic therapy and radiation therapy

International Nuclear Information System (INIS)

Chen Na; Tu Yu; Zhang Xuguang

2010-01-01

This paper describes a novel treatment: based on nanoparticles that combines radiotherapy and photodynamic therapy. With this approach, the application of traditional photodynamic therapies only to surface treatment can be solved, so that the therapeutic effect can be improved; the approach also could guarantee the effectiveness of treatment and reduce radiation doses, so it can effectively control the complications of radiotherapy, This new modality will open a new chapter for cancer therapy. (authors)
WHO HAS THERAPY-RELATED AML?

Directory of Open Access Journals (Sweden)

Robert Gale

2017-03-01

Full Text Available Therapy-related leukemia or therapy-related myeloid neoplasm are widely-used terms to designate leukemia developing in persons who previously received anti-cancer therapy (for example, see references 1, 2, especially if the prior anti-cancer therapy included drugs such as alkylators, DNA-intercalators, topoisomerase-2-inhibitors, purines and/or ionizing radiations. Sometimes specific genes such as AML1, EVI1, NRAS or MLL are mutated by therapy or gene variants are produced which activate mutagens or interfere with DNA repair, such FANC, NQ01 or AML2. 3-5 But how can we know if AML in someone is a therapy-related? Keywords: Therapy-related leukemia; alkylators; ionizing radiations; Topoisomerase Inhibitors; DNA Repair

Radiation therapy for digestive tumors

International Nuclear Information System (INIS)

Piedbois, P.; Levy, E.; Thirion, P.; Martin, L.; Calitchi, E.; Otmezguine, Y.; Le Bourgeois, J.P.

1995-01-01

This brief review of radiation therapy of digestive tumors in 1994 seeks to provide practical answers to the most commonly asked questions: What is the place of radiation therapy versus chemotherapy for the treatment of these patients ? What are the approved indications of radiation therapy and which avenues of research are being explored ? Radiation therapy is used in over two-thirds of patients referred to an oncology department for a gastrointestinal tract tumor. The main indications are reviewed: cancer of the rectum and anal canal and, to a lesser extent, cancer of the esophagus and pancreas. The main focuses of current research include radiation therapy-chemotherapy combinations, intraoperative radiation therapy, and radiation therapy of hepatobiliary tumors. (authors). 23 refs., 1 fig
Music therapy career aptitude and generalized self-efficacy in music therapy students.

Science.gov (United States)

Lim, Hayoung A; Befi, Cathy M

2014-01-01

While the Music Therapy Career Aptitude Test (MTCAT) provides a measure of student aptitude, measures of perceived self-efficacy may provide additional information about a students' suitability for a music therapy career. As a first step in determining whether future studies examining combined scores from the MTCAT and the Generalized Self-Efficacy (GSE) scale would be useful to help predict academic success in music therapy, we explored the internal reliability of these two measures in a sample of undergraduate students, and the relationship (concurrent validity) of the measures to one another. Eighty undergraduate music therapy students (14 male; 66 female) completed the MTCAT and GSE. To determine internal reliability we conducted tests of normality and calculated Cronbach's Coefficient Alpha for each measure. Pearson correlation coefficients were calculated to ascertain the strength of the relationship between the MTCAT and GSE. MTCAT scores were normally distributed and had high internal consistency (Cronbach's α = 0.706). GSE scores were not normally distributed, but had high internal consistency (Cronbach's α = 0.748). The correlation coefficient analysis revealed that MTCAT and GSE scores were moderately correlated ((r = 0.426, p music therapy students; however, a more complete picture of student suitability for music therapy may be determined by administering the GSE alongside the MTCAT. Future studies are needed to determine whether combined MTCAT and GSE scores can be used to predict student success in an undergraduate music therapy program. © the American Music Therapy Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Massage therapy research review.

Science.gov (United States)

Field, Tiffany

2016-08-01

In this review, massage therapy has been shown to have beneficial effects on varying conditions including prenatal depression, preterm infants, full-term infants, autism, skin conditions, pain syndromes including arthritis and fibromyalgia, hypertension, autoimmune conditions including asthma and multiple sclerosis, immune conditions including HIV and breast cancer and aging problems including Parkinson's and dementia. Although many of the studies have involved comparisons between massage therapy and standard treatment control groups, several have compared different forms of massage (e.g. Swedish versus Thai massage), and different active therapies such as massage versus exercise. Typically, the massage therapy groups have experienced more positive effects than the control or comparison groups. This may relate to the massage therapy providing more stimulation of pressure receptors, in turn enhancing vagal activity and reducing cortisol levels. Some of the researchers have assessed physical, physiological and biochemical effects, although most have relied exclusively on self-report measures. Despite these methodological problems and the dearth of research from the U.S., the massage therapy profession has grown significantly and massage therapy is increasingly practiced in traditional medical settings, highlighting the need for more rigorous research. Copyright © 2016 Elsevier Ltd. All rights reserved.
Tumor therapy and pregnancy

International Nuclear Information System (INIS)

Joss, R.; Brunner, K.W.

1982-01-01

Many successfully treated tumour patients are children and juveniles. This raises questions as to the effects of tumour therapy on reproductiveness and offspring. The possible extent of damage to the male and female gonads caused by surgical, chemical, and radiological tumour therapy is investigated. Also, the problem of tumour therapy or women developing neoplasms during pregnancy. Pregnancies after successful tumour therapy are quite frequent today. Experience so far suggests that the rate of congenital deformities is not significantly increased. (orig.) [de
Effect of methyl parathion on the muscle and brain acetylcholinesterase activity of matrinxã (Brycon cephalus

Directory of Open Access Journals (Sweden)

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.
Postponed effect of neostigmine on oxidative homeostasis

Directory of Open Access Journals (Sweden)

Pohanka Miroslav

2014-09-01

Full Text Available Cholinesterases are enzymes able to hydrolyze the neurotransmitter acetylcholine and thus to terminate transmission. Once the enzymes are inhibited, excitotoxicity can appear in the adjacent cells. It is well known that oxidative stress is involved in the toxicity of cholinesterase inhibitors. Commonly, stress follows inhibition of cholinesterases and disappears shortly afterwards. In the present experiment, it was decided to test the impact of an inhibitor, neostigmine, on oxidative stress in BALB/c mice after a longer interval. The animals were sacrificed three days after onset of the experiment and spleens and livers were collected. Reduced glutathione (GSH, glutathione reductase (GR, glutathione S-transferase (GST, thiobarbituric acid reactive substances (TBARS, ferric reducing antioxidant power (FRAP, caspase-3 and activity of acetylcholinesterase (AChE were assayed. The tested markers were not altered with exceptions of FRAP. The FRAP values indicate accumulation of low molecular weight antioxidants in the examined organs. The role of low molecular weight antioxidants in the toxicity of AChE inhibitors is discussed.
Effect of the Protection of the Residual Aminopropyl Groups of a Chiral Stationary Phase Based on (+)-(18-Crown-6)-2,3,11,12-tetracarboxylic Acid on the Chiral Resolution Behaviors

International Nuclear Information System (INIS)

Hyun, Myung Ho; Kim, Young Hwa; Cho, Yoon Jae

2004-01-01

The protection of the unreacted residual aminopropyl groups of CSP 2 was found to improve the retention and the resolution factors for the resolution of racemic compounds containing a primary amino group. However, the size of the protecting acyl group should not be too bulky. As a protecting acyl group, acetyl or butyryl group seems to be good enough for the improved retention and the improved resolution. However, the separation factors were found to decrease slightly when the unreacted residual aminopropyl groups of the CSP are protected by an acyl group.
Effect of the Protection of the Residual Aminopropyl Groups of a Chiral Stationary Phase Based on (+)-(18-Crown-6)-2,3,11,12-tetracarboxylic Acid on the Chiral Resolution Behaviors

Energy Technology Data Exchange (ETDEWEB)

Hyun, Myung Ho; Kim, Young Hwa; Cho, Yoon Jae [Pusan National University, Busan (Korea, Republic of)

2004-03-15

The protection of the unreacted residual aminopropyl groups of CSP 2 was found to improve the retention and the resolution factors for the resolution of racemic compounds containing a primary amino group. However, the size of the protecting acyl group should not be too bulky. As a protecting acyl group, acetyl or butyryl group seems to be good enough for the improved retention and the improved resolution. However, the separation factors were found to decrease slightly when the unreacted residual aminopropyl groups of the CSP are protected by an acyl group.
Decreased colonization of fecal Clostridium coccoides/Eubacterium rectale species from ulcerative colitis patients in an in vitro dynamic gut model with mucin environment

DEFF Research Database (Denmark)

Vermeiren, Joan; Van den Abbeele, Pieter; Laukens, Debby

2012-01-01

in-depth community analysis of those microbial groups known to produce butyrate revealed that the diversity of the Clostridium coccoides/Eubacterium rectale and Clostridium leptum group, and counts of Faecalibacterium prausnitzii were lower in the luminal fractions of the UC samples. Counts...... of Roseburia spp. were lower in the mucosal fractions of the UC samples. qPCR analysis for butyryl-CoA:acetate CoA transferase, responsible for butyrate production, displayed a lower abundance in both the luminal and mucosal fractions of the UC samples. The M-SHIME model revealed depletion in butyrate...
Evaluation of Inter Therapy

DEFF Research Database (Denmark)

Pedersen, Inge Nygaard

2002-01-01

This article (revised conference lecture from the 10th World Congress of Music Therapy, Oxford July 2002)) emphasizes the evaluation of the training of Inter Therapy for music therapy students at the MA training at Aalborg University. The students take turns in being client and therapist within...
Fertility and cancer therapy

International Nuclear Information System (INIS)

Maguire, L.C.

1979-01-01

With increased survival of increasing numbers of cancer patients as a result of therapy, the consequences, early and late, of the therapies must be realized. It is the treating physician's duty to preserve as much reproductive potential as possible for patients, consistent with adequate care. With radiotherapy this means shielding the gonads as much as possible, optimal but not excessive doses and fields, oophoropexy, or sperm collection and storage prior to irradiation. With chemotherapy it means the shortest exposure to drugs consistent with best treatment and prior to therapy the collection and storage of sperm where facilities are available. At present this is still an experimental procedure. Artificial insemination for a couple when the male has received cancer therapy is another alternative. Finally, it is the responsibility of physicians caring for patients with neoplasms to be knowledgeable about these and all other effects of therapy so that patients may be counseled appropriately and understand the implications of therapy for their life
Complementary therapies in social psychiatry

DEFF Research Database (Denmark)

Lunde, Anita; Dürr, Dorte Wiwe

three residential homes (n= 51 / 91 respondents - response rate 56 %) shows that the most common used complementary therapy is music therapy 43%, and only 10% of residents do not use these therapies at all. Overall, 43% of residents strongly agree, that these therapies strengthens their recovery process...
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
Accelerators for cancer therapy

International Nuclear Information System (INIS)

Lennox, Arlene J.

2000-01-01

The vast majority of radiation treatments for cancerous tumors are given using electron linacs that provide both electrons and photons at several energies. Design and construction of these linacs are based on mature technology that is rapidly becoming more and more standardized and sophisticated. The use of hadrons such as neutrons, protons, alphas, or carbon, oxygen and neon ions is relatively new. Accelerators for hadron therapy are far from standardized, but the use of hadron therapy as an alternative to conventional radiation has led to significant improvements and refinements in conventional treatment techniques. This paper presents the rationale for radiation therapy, describes the accelerators used in conventional and hadron therapy, and outlines the issues that must still be resolved in the emerging field of hadron therapy
Hadron Therapy for Cancer Treatment

International Nuclear Information System (INIS)

Lennox, Arlene

2003-01-01

The biological and physical rationale for hadron therapy is well understood by the research community, but hadron therapy is not well established in mainstream medicine. This talk will describe the biological advantage of neutron therapy and the dose distribution advantage of proton therapy, followed by a discussion of the challenges to be met before hadron therapy can play a significant role in treating cancer. A proposal for a new research-oriented hadron clinic will be presented.
Prognostic Factors of Organophosphate Poisoning Between the Death and Survival Groups

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Tzeng-Jih Lin

2007-04-01

Full Text Available In this prospective case series study, we consider the different factors between death and survival groups of organophosphate poisoning. Patients in tertiary-care medical center who had been exposed to organophosphate were included in the study. Pralidoxime (PAM was discontinued after atropine had controlled the clinical situation. We recorded the demographic data, amount of organophosphate consumption, duration of coma, duration of ventilator use, duration of hospitalization, findings of chest X-ray, white blood cell count, acetylcholinesterase concentration, plasma cholinesterase concentration, total atropine amount, duration of atropine use, total PAM amount, duration of PAM use, urine organophosphate peak concentration, duration of urine organophosphate and mortality rate. Urine was collected every 8 hours and was analyzed by gas chromatography equipped with a flame photometric detector and gas chromatography with mass spectrometer detector for organophosphate determination. The urine organophosphate peak concentration was recorded. Wilcoxon rank sum test was used to compare the factors between death and survival groups. Fisher's exact test was used to compare the different findings of chest X-ray between the death and survival groups. Evidently, the death group had a higher amount of organophosphate consumption, duration of coma, and higher white blood cell count than those in the survival group. Also, the death group had lower duration of hospitalization, and decreased concentrations of acetylcholinesterase and plasma cholinesterase. Total PAM amount use and duration of PAM use were lower. However, the duration of ventilator use, findings of chest X-ray, total atropine amount, duration of atropine, urine organophosphate peak concentration and duration of urine organophosphate were similar in both groups. The mortality rate of our 50 cases was 20%. As stated earlier, the cases of the death group had insufficient PAM therapy. The maximum
The ethics of gene therapy.

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Chan, Sarah; Harris, John

2006-10-01

Recent developments have progressed in areas of science that pertain to gene therapy and its ethical implications. This review discusses the current state of therapeutic gene technologies, including stem cell therapies and genetic modification, and identifies ethical issues of concern in relation to the science of gene therapy and its application, including the ethics of embryonic stem cell research and therapeutic cloning, the risks associated with gene therapy, and the ethics of clinical research in developing new therapeutic technologies. Additionally, ethical issues relating to genetic modification itself are considered: the significance of the human genome, the distinction between therapy and enhancement, and concerns regarding gene therapy as a eugenic practice.
Gene therapy of thyroid carcinoma

International Nuclear Information System (INIS)

Zheng Wei; Tan Jian

2007-01-01

Normally, differentiated thyroid carcinoma(DTC) is a disease of good prognosis, but about 30% of the tumors are dedifferentiate, which are inaccessible to standard therapeutic procedures such as 'operation, 131 I therapy and thyroid hormone'. Both internal and abroad experts are researching a new therapy of dedifferentiated thyroid carcinoma--gene therapy. Many of them utilize methods of it, but follow different strategies: (1) transduction of the thyroid sodium/iodide transporter gene to make tissues that do not accumulate iodide treatable by 131 I therapy; (2) strengthening of the anti-tumor immune response; (3) suicide gene therapy; (4) depression the generation of tumor cells; (5) gene therapy of anti- vascularization. (authors)
Diagnosis and treatment of dementia: 6. Management of severe Alzheimer disease.

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Herrmann, Nathan; Gauthier, Serge

2008-12-02

resources are essential. Severe Alzheimer disease requires frequent monitoring by health professionals. Simple nonpharmacologic approaches may address problems with mood and agitation. Antipsychotic drug therapy is occasionally necessary despite the inherent risks. Therapy with a cholinesterase inhibitor and memantine may be useful for selected patients.
Immune control of HIV-1 infection after therapy interruption: immediate versus deferred antiretroviral therapy

Directory of Open Access Journals (Sweden)

Bernaschi Massimo

2009-10-01

Full Text Available Abstract Background The optimal stage for initiating antiretroviral therapies in HIV-1 bearing patients is still a matter of debate. Methods We present computer simulations of HIV-1 infection aimed at identifying the pro et contra of immediate as compared to deferred Highly Active Antiretroviral Therapy (HAART. Results Our simulations highlight that a prompt specific CD8+ cytotoxic T lymphocytes response is detected when therapy is delayed. Compared to very early initiation of HAART, in deferred treated patients CD8+ T cells manage to mediate the decline of viremia in a shorter time and, at interruption of therapy, the virus experiences a stronger immune pressure. We also observe, however, that the immunological effects of the therapy fade with time in both therapeutic regimens. Thus, within one year from discontinuation, viral burden recovers to the value at which it would level off in the absence of therapy. In summary, simulations show that immediate therapy does not prolong the disease-free period and does not confer a survival benefit when compared to treatment started during the chronic infection phase. Conclusion Our conclusion is that, since there is no therapy to date that guarantees life-long protection, deferral of therapy should be preferred in order to minimize the risk of adverse effects, the occurrence of drug resistances and the costs of treatment.

Music therapy for depression.

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Aalbers, Sonja; Fusar-Poli, Laura; Freeman, Ruth E; Spreen, Marinus; Ket, Johannes Cf; Vink, Annemiek C; Maratos, Anna; Crawford, Mike; Chen, Xi-Jing; Gold, Christian

2017-11-16

Depression is a highly prevalent mood disorder that is characterised by persistent low mood, diminished interest, and loss of pleasure. Music therapy may be helpful in modulating moods and emotions. An update of the 2008 Cochrane review was needed to improve knowledge on effects of music therapy for depression. 1. To assess effects of music therapy for depression in people of any age compared with treatment as usual (TAU) and psychological, pharmacological, and/or other therapies.2. To compare effects of different forms of music therapy for people of any age with a diagnosis of depression. We searched the following databases: the Cochrane Common Mental Disorders Controlled Trials Register (CCMD-CTR; from inception to 6 May 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; to 17 June 2016); Thomson Reuters/Web of Science (to 21 June 2016); Ebsco/PsycInfo, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, and PubMed (to 5 July 2016); the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, the National Guideline Clearing House, and OpenGrey (to 6 September 2016); and the Digital Access to Research Theses (DART)-Europe E-theses Portal, Open Access Theses and Dissertations, and ProQuest Dissertations and Theses Database (to 7 September 2016). We checked reference lists of retrieved articles and relevant systematic reviews and contacted trialists and subject experts for additional information when needed. We updated this search in August 2017 and placed potentially relevant studies in the "Awaiting classification" section; we will incorporate these into the next version of this review as appropriate. All randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing music therapy versus treatment as usual (TAU), psychological therapies, pharmacological therapies, other therapies, or different forms of music therapy for reducing depression. Two review
Nanomedicine and cancer therapies

CERN Document Server

Sebastian, Mathew; Ninan, Neethu

2012-01-01

Nanotechnology has the power to radically change the way cancer is diagnosed, imaged, and treated. The holistic approach to cancer involves noninvasive procedures that emphasize restoring the health of human energy fields. Presenting a wealth of information and research about the most potent cancer healing therapies, this forward-thinking book explores how nanomedicine, holistic medicine, and other cancer therapies play important roles in treatment of this disease. Topics include nanobiotechnology for antibacterial therapy and diagnosis, mitochondrial dysfunction and cancer, antioxidants and combinatorial therapies, and optical and mechanical investigations of nanostructures for biomolecular detection.
Comparison of Women Who Enter Feminist Therapy and Women Who Enter Traditional Therapy.

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Marecek, Jeanne; And Others

1979-01-01

Compared women in feminist v traditional therapy. There were no differences on demographic characteristics. Clients of feminist therapists were more likely to describe their political views as radical and to identify with members of the women's movements. They rated therapy as more helpful than clients of traditional therapy. (Author)
Play Therapy: A Review

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Porter, Maggie L.; Hernandez-Reif, Maria; Jessee, Peggy

2009-01-01

This article discusses the current issues in play therapy and its implications for play therapists. A brief history of play therapy is provided along with the current play therapy approaches and techniques. This article also touches on current issues or problems that play therapists may face, such as interpreting children's play, implementing…
Music Therapy and Avatars: Reflections on Virtual Learning Environments for Music Therapy Students

DEFF Research Database (Denmark)

Story, Maya

2014-01-01

Music therapy students have expressed concerns regarding their general preparedness for practicum and working with new populations. Simulations in the immersive virtual world, Second Life, may provide a platform to assist in training music therapy students and enhance preparedness. This project...... examined the feasibility of utilizing Second Life to assist in training music therapists. Music therapy practicum students enrolled in a music therapy equivalency program participated in weekly one hour virtual class meetings in Second Life, which included 5 sessions of music therapy simulations....... At the end of the semester, students were interviewed in relation to their experiences, and interviews were analyzed qualitatively. Common themes among students were limitations of Second Life software, student’s knowledge of software, emotional reactions (both positive and negative), and distance learning....
Scientific perspectives on music therapy.

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Hillecke, Thomas; Nickel, Anne; Bolay, Hans Volker

2005-12-01

What needs to be done on the long road to evidence-based music therapy? First of all, an adequate research strategy is required. For this purpose the general methodology for therapy research should be adopted. Additionally, music therapy needs a variety of methods of allied fields to contribute scientific findings, including mathematics, natural sciences, behavioral and social sciences, as well as the arts. Pluralism seems necessary as well as inevitable. At least two major research problems can be identified, however, that make the path stony: the problem of specificity and the problem of eclecticism. Neuroscientific research in music is giving rise to new ideas, perspectives, and methods; they seem to be promising prospects for a possible contribution to a theoretical and empirical scientific foundation for music therapy. Despite the huge heterogeneity of theoretical approaches in music therapy, an integrative model of working ingredients in music therapy is useful as a starting point for empirical studies in order to question what specifically works in music therapy. For this purpose, a heuristic model, consisting of five music therapy working factors (attention modulation, emotion modulation, cognition modulation, behavior modulation, and communication modulation) has been developed by the Center for Music Therapy Research (Viktor Dulger Institute) in Heidelberg. Evidence shows the effectiveness of music therapy for treating certain diseases, but the question of what it is in music therapy that works remains largely unanswered. The authors conclude with some questions to neuroscientists, which we hope may help elucidate relevant aspects of a possible link between the two disciplines.
Complementary Pancreatitis Therapies

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... medication, and improve quality of life.1,2 Massage Therapy Massage therapy involves touch and different techniques of stroking ... of the body or be a full-body massage. Massage can be performed through one’s clothing or ...
Neutron therapy

International Nuclear Information System (INIS)

Riesler, Rudi

1995-01-01

Standard radiotherapy uses Xrays or electrons which have low LET (linear energy transfer); in contrast, particles such as neutrons with high LET have different radiobiological responses. In the late 1960s, clinical trials by Mary Catterall at the Hammersmith Hospital in London indicated that fast neutron radiation had clinical advantages for certain malignant tumours. Following these early clinical trials, several cyclotron facilities were built in the 1980s for fast neutron therapy, for example at the University of Washington, Seattle, and at UCLA. Most of these newer machines use extracted cyclotron proton beams in the range 42 to 66 MeV with beam intensities of 15 to 60 microamps. The proton beams are transported to dedicated therapy rooms, where neutrons are produced from beryllium targets. Second-generation clinical trials showed that accurate neutron beam delivery to the tumour site is more critical than for photon therapy. In order to achieve precise beam geometries, the extracted proton beams have to be transported through a gantry which can rotate around the patient and deliver beams from any angle; also the neutron beam outline (''field shape'') must be adjusted to extremely irregular shapes using a flexible collimation system. A therapy procedure has to be appropriately organized, with physicians, radiotherapists, nurses, medical physicists and other staff in attendance; other specialized equipment, such as CT or MRI scanners and radiation simulators must be made available. Neutron therapy is usually performed only in radiation oncology departments of major medical centres
Music therapy in dementia

DEFF Research Database (Denmark)

McDermott, Orii; Crellin, Nadia; Ridder, Hanne Mette Ochsner

2013-01-01

Objective Recent reviews on music therapy for people with dementia have been limited to attempting to evaluate whether it is effective, but there is a need for a critical assessment of the literature to provide insight into the possible mechanisms of actions of music therapy. This systematic review......, five studies investigated hormonal and physiological changes, and five studies focused on social and relational aspects of music therapy. The musical interventions in the studies were diverse, but singing featured as an important medium for change. Conclusions Evidence for short-term improvement...... in mood and reduction in behavioural disturbance was consistent, but there were no high-quality longitudinal studies that demonstrated long-term benefits of music therapy. Future music therapy studies need to define a theoretical model, include better-focused outcome measures, and discuss how the findings...
Adlerian Marriage Therapy.

Science.gov (United States)

Carlson, Jon; Dinkmeyer, Don, Sr.

1987-01-01

Describes the assumptions, processes, and techniques used in Alderian marriage therapy. Describes purpose of therapy as assessing current beliefs and behaviors while educating the couple in new procedures that can help the couple establish new goals. (Author/ABL)
Therapy of hyperthyroidism

International Nuclear Information System (INIS)

Wildmeister, W.

1982-01-01

The etiology of hyperthyroidism is still largely unknown and therefore no causal therapy of this condition is possible. Antithyroid drug treatment is usually carried out with thiocarbamides. When an euthyroid state is achieved synthetic thyroid hormones are added. Pregnancy and iodine contamination (after exposure to contrast medium) require individual treatment. In this paper the advantages, indications and contraindications are discussed as well as supportive drug therapy necessary in specific cases. Radioiodine therapy is reserved for patients over 35 years of age; the individual dose is calculated according to the size of the thyroid gland and the iodine uptake. Disadvantageous is the late onset of therapeutic efficiency, the small effect on the size of goitre and the exposure to radiation. A patient should be operated upon in an euthyroid state, i.e. after preoperative drug therapy. Operations are normally performed on individuals with a coexistent goitre or where antithyroid drugs or radioiodine therapy are contraindicated. Paresis of the recurrent laryngeal nerve and hypoparathyroidism are rare complications. 3 to 4 g of thyroid tissues should remain. Of great importance in all cases are precise diagnostics both before and after commencing treatment and adequate follow up. (orig./MG) [de
Improving access to psychological therapies in voice disorders: a cognitive behavioural therapy model.

Science.gov (United States)

Miller, Tracy; Deary, Vincent; Patterson, Jo

2014-06-01

The improving access to psychological therapies initiative has highlighted the importance of managing mental health problems effectively, and research has shown excellent outcomes from cognitive behavioural therapy (CBT) interventions. Patients presenting with functional dysphonia will often also describe psychological distress including anxiety, depression and reduced general well-being, and it is felt that effective voice therapy needs to include the management of psychological well-being. The evidence for the use of CBT enhanced voice therapy is limited to date. Recent research has only started to identify the benefits of this approach and questions regarding how to achieve and maintain competence are essential. Voice therapy outcomes are positive and patients receiving CBT with voice therapy have shown more improvement in their general well-being and distress. CBT is a very well evidenced therapy and recommended by The National Institute for Health and Care Excellence (NICE) as the treatment of choice for mental health difficulties and medically unexplained symptoms. Allied health professionals are increasingly being trained to use CBT skills in the management of a number of symptoms/illnesses, and this should be considered for the management of functional dysphonia. However, there is a need for more research and detailed consideration of how therapists should be trained and supervised and how cost-effective this approach may be.
Spectrum of Art Therapy Practice: Systematic Literature Review of "Art Therapy," 1983-2014

Science.gov (United States)

Potash, Jordan S.; Mann, Sarah M.; Martinez, Johanna C.; Roach, Ann B.; Wallace, Nina M.

2016-01-01

The objective of this study was to determine art therapists' fit in the continuum of health delivery services defined by behavioral health. All publications in "Art Therapy: Journal of the American Art" Therapy Association from 1983 (Volume 1) to 2014 (Volume 31) were systematically reviewed to understand how art therapy has been…
Effectiveness of medication / auricular therapy / phyto-therapy combination in the treatment of hypertensive patients

Directory of Open Access Journals (Sweden)

José Ramón Martínez Pérez

2015-10-01

Full Text Available Background: hypertension is one of the main cardiovascular risk factors, so its control improves the life expectancy of patients.Objective: to assess the effects of a treatment combining medication with auricular therapy and phyto-therapy in hypertensive patients assisted at the health area of ”Romárico Oro” Polyclinic, in Puerto Padre, Las Tunas province.Methods: an intervention study was carried out in 68 hypertensive patients of the health area of “Romárico Oro” Polyclinic in Puerto Padre from April, 2013 to April, 2014. The patients were distributed at random into two equal groups; the first received medication combined with auricular therapy and phyto-therapy, while the second one received only medication. The statistical analysis was done by means of Statistic system, t-student and Chi-Square tests were used and p< or =0.05 was considered as level of statistical significance.Results: by the end of the intervention, 73, 53% of the patients of the group with the combination of drug treatment and auricular therapy and phyto-therapy were controlled. In this group, the diastolic filling pressure diminished to 2, 2 mm Hg and the systolic gradient to 3, 66 mm, regarding the group treated only with drugs. Only one patient, representing the 2, 94% showed adverse reaction to the natural and traditional treatment.Conclusions: the combination of medication with auricular therapy and phyto-therapy proved to be effective, corroborated by a significant decrease of quantity of crisis, diastolic and systolic filling pressure values and increase of number of patients with their disease controlled; the report of only one complication shows the innocuousness of the auricular therapy and phyto-therapy treatment.
Translation of the Speech Therapy Programs in the Logomon Assisted Therapy System

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SCHIPOR, D. M.

2010-05-01

Full Text Available This interdisciplinary research was developed with a view to create and implement an intelligent informatics system for the treatment of dyslalic disorders, specific to the Romanian language (CBTS system - computer-based speech therapy, as a complementary speech therapy method, customised and client-oriented. The rules of the logotherapeutic guide have been expressed in pseudocode programs in order to allow a greater flexibility in expressing the logotherapeutic procedures in an informatics system. The pseudocode logopedic programs comprise the succession of stages of the therapeutic program from a speech therapy perspective, and based on what the expert system can achieve. The LOGOMON system is conceived in order to assist the physical therapist and the child during the entire therapeutic period, recording the main data related to the child, which proved to be useful in diagnosis and treatment. The experimental validation of the system proved that assisted therapy contributes to the improvement of classical therapy, to obtaining optimal results in correcting the dyslalic person's speech.
A review study on medicinal plants affecting amnesia through cholinergic system

Directory of Open Access Journals (Sweden)

Baradaran Azar

2012-01-01

Full Text Available Neurotransmitter modification is an important method for the treatment of memory loss or amnesia. Cholinomimetic drugs, particularly, acetylcholine esterase inhibitors are the mainstream in pharmacotherapy of amnesia. Donepezil, tacrine, galantamine, and rivastigmine are cholinesterase inhibitors which are widely used in the treatment of amnesia, however, their therapeutic effects are not significant. Therefore, other possibilities including herbal medicine sources have been considered for memory loss therapy. There are some Medicinal plants with cholinomimetic property which mostly possess antioxidant activity, too. These plants may not only ameliorate amnesia but also can be a good source for drug discovery. In this paper other than introducing the medicinal plants and their components affective on cholinergic system and effective on memory loss, their probable advantages over synthetic drugs are discussed.
Implication of coumarins towards central nervous system disorders.

Science.gov (United States)

Skalicka-Woźniak, Krystyna; Orhan, Ilkay Erdogan; Cordell, Geoffrey A; Nabavi, Seyed Mohammad; Budzyńska, Barbara

2016-01-01

Coumarins are widely distributed, plant-derived, 2H-1-benzopyran-2-one derivatives which have attracted intense interest in recent years as a result of their diverse and potent pharmacological properties. Particularly, their effects on the central nervous system (CNS) have been established. The present review discusses the most important pharmacological effects of natural and synthetic coumarins on the CNS, including their interactions with benzodiazepine receptors, their dopaminergic and serotonergic affinity, and their ability to inhibit cholinesterases and monoamine oxidases. The structure-activity relationships pertaining to these effects are also discussed. This review posits that natural or synthetic coumarins have the potential for development in the therapy of psychiatric and neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, schizophrenia, anxiety, epilepsy, and depression. Copyright © 2015 Elsevier Ltd. All rights reserved.
Why commercialization of gene therapy stalled; examining the life cycles of gene therapy technologies.

Science.gov (United States)

Ledley, F D; McNamee, L M; Uzdil, V; Morgan, I W

2014-02-01

This report examines the commercialization of gene therapy in the context of innovation theories that posit a relationship between the maturation of a technology through its life cycle and prospects for successful product development. We show that the field of gene therapy has matured steadily since the 1980s, with the congruent accumulation of >35 000 papers, >16 000 US patents, >1800 clinical trials and >$4.3 billion in capital investment in gene therapy companies. Gene therapy technologies comprise a series of dissimilar approaches for gene delivery, each of which has introduced a distinct product architecture. Using bibliometric methods, we quantify the maturation of each technology through a characteristic life cycle S-curve, from a Nascent stage, through a Growing stage of exponential advance, toward an Established stage and projected limit. Capital investment in gene therapy is shown to have occurred predominantly in Nascent stage technologies and to be negatively correlated with maturity. Gene therapy technologies are now achieving the level of maturity that innovation research and biotechnology experience suggest may be requisite for efficient product development. Asynchrony between the maturation of gene therapy technologies and capital investment in development-focused business models may have stalled the commercialization of gene therapy.
Biological therapies for spondyloarthritis.

Science.gov (United States)

Bruner, Vincenzo; Atteno, Mariangela; Spanò, Angelo; Scarpa, Raffaele; Peluso, Rosario

2014-06-01

Biological therapies and new imaging techniques have changed the therapeutic and diagnostic approach to spondyloarthritis. In patients with axial spondyloarthritis, tumor necrosis factor α (TNFα) inhibitor treatment is currently the only effective therapy in patients for whom conventional therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) has failed. TNFα inhibitor treatment is more effective in preventing articular damage in peripheral joints than in axial ones. It is important to treat patients at an early stage of disease to reduce disease progression; moreover it is necessary to identify causes of therapy inefficacy in preventing joint damage in the axial subset.
Individualized therapies in colorectal cancer: KRAS as a marker for response to EGFR-targeted therapy

Directory of Open Access Journals (Sweden)

Li Kuiyuan

2009-04-01

Full Text Available Abstract Individualized therapies that are tailored to a patient's genetic composition will be of tremendous value for treatment of cancer. Recently, Kirsten ras (KRAS status has emerged as a predictor of response to epidermal growth factor receptor (EGFR targeted therapies. In this article, we will discuss targeted therapies for colorectal cancers (CRC based on EGFR signaling pathway and review published data about the potential usefulness of KRAS as a biological marker for response to these therapies. Results from relevant studies published since 2005 and unpublished results presented at national meetings were retrieved and summarized. These studies reflected response (or lack of response to EGFR-targeted therapies in patients with metastatic CRC as a function of KRAS status. It has become clear that patients with colorectal cancer whose tumor has an activating mutation in KRAS do not respond to monoclonal antibody therapies targeting EGFR. It should now become a standard practice that any patients being considered for EGFR targeted therapies have their tumors tested for KRAS status and only those with wild-type KRAS being offered such therapies.

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