Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The following parameters were determined in blood serum of apparently healthy Bennett's wallabies (Macropus rufogriseus) using the Hitachi 917 (Roche Diagnostics, Mannheim, Germany) and/or the Vettest 8008 (IDEXX-GmbH, Woerrstadt, Germany): alkaline phosphatase, alanine aminotransferase, ammonia, alpha-amylase, aspartate aminotransferase, Ca, Cl, cholesterol, cholinesterase, creatine kinase, creatinine, gammaglutamyltransferase, glucose, iron, lactate dehydrogenase, magnesium, phosphate, potassium, protein, sodium, total bilirubin, triglyceride, and urea. The results for cholesterol, glucose, total protein, triglyceride and for the enzymes alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyltransferase and lactate dehydrogenase differed significantly between both methods (P < 0.05). There is a negative correlation between the age of the Bennett's wallabies and the activity of the alkaline phosphatase. Five protein fractions could be separated on cellulose acetate electrophoresis. The mean concentrations of fructosamine and beta-hydroxybutyrate were 447.3 micromol/L and 0.27 mmol/L, respectively. The estimated vitamin A intake had no influence on the vitamin A concentration in serum. The serum vitamin E concentration was in general low and vitamin E was below the detection limit of 0.82 micromol/L in 29 out of 42 serum samples. The use of these analytes is discussed concerning the knowledge about the physiology, nutrition and diseases of macropods.
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PMID:On the clinical chemistry of the Bennett's wallaby (Macropus rufogriseus rufogriseus). 1685 6

The therapeutic use of enzyme inhibitors in treatment of neurodegenerative diseases has its origin in the anti Parkinson action of the selective monoamine oxidase (MAO) B inhibitor, l-deprenyl (selegiline ), a failed anti depressant in 1975. This led to further development of MAO- A and B, catechol-O-methyltansferase and cholinestrerase inhibitors as anti Parkinson and Alzheimer drugs. One of the main reasons for the cognitive deficit in dementia of the Alzheimer' type (AD) and in dementia with Lewy bodies (DLB) is degeneration of cholinergic cortical neurones and synaptic plasticity. This led to a correlation that similar to Parkinson's Disease (PD), cholinesterase inhibitors (ChEI) may also have therapeutic activity in AD. Significant percentage of AD and DLB subjects also nigrostriatal dopaminergic, locus ceruleous noradrenergic and raphe nucleus serotoninergic neurones. The present ChEI anti AD drugs have limited symptomatic activity and devoid of neuroprotective property that is needed for disease modifying action. It is becoming clear that there are no magic bullets for neurodegenerative disorders and shut gun approach is needed either as polypharmacology or drugs with multiple activity at different target sites in the CNS. The complex pathology of AD as well as cascade of events that leads to the neurodegenerative process has led us to develop several multifunctional neuroprotective drugs with several CNS targets with possible disease modifying activity. Employing the pharamcophore of our antiparkinson drug rasagiline (Azilect, Agilect, N-propagrgyl-1R-aminoindan) we have developed a novel multifunctional neuroprotective drug, ladostigil [TV-3326 (N-propargyl-3R-aminoindan-5yl)-ethyl methylcarbamate)], with both cholinesterase-butyrylesterase (Ch-BuE) and brain selective monoamine-oxidase (MAO) AB inhibitory activities possessing the neuroprotective-neurescue propargyl moiety, as potential treatment of AD and DLB and PD with dementias. Since brain MAO and iron increase in AD, PD and ageing, that could lead to iron dependent oxidative stress neurodegeneration, we have developed another series of multifunctional drugs (M30 HLA-20 series) which are brain permeable iron chelators- brain selective MAO inhibitors and possess the propargyl neuroprotective moiety. These series of drugs have the ability of regulating and processing APP (amyloid precursor protein) and reducing Abeta peptide, since APP is a metaloprotein, with an iron responsive element 5d'UTR similar to transferring and ferritin.
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PMID:The path from anti Parkinson drug selegiline and rasagiline to multifunctional neuroprotective anti Alzheimer drugs ladostigil and m30. 1716 53

The recent therapeutic approach in which drug candidates are designed to possess diverse pharmacological properties and act on multiple targets has stimulated the development of several multifunction drugs. These include ladostigil (TV3326) [(N-propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate], which combines the pharmacophore-neuroprotective effects of rasagiline, a selective monoamine oxidase (MAO)-B inhibitor, with the cholinesterase (ChE) inhibitory activity of rivastigmine or iron chelating moiety such as M30. In the case of M30 the pharmacophore of brain permeable iron chelator VK-28 plus the MAO inhibitor-neuroprotective propargylamine moiety of rasagiline are combined in a single molecule as a potential treatment for Alzheimer's disease, Lewy body disease, and Parkinson's disease with dementia. Here, we discuss the activities of ladostigil in terms of its cholinesterase cognitive enhancing potential, antiParkinson, antidepressant, neuroprotection and APP (amyloid precursor protein) processing potential. One major attribute of ladostigil is its neuroprotective activity in neuronal cell cultures and in vivo. Employing an apoptotic model of neuroblastoma SK-N-SH cells, the molecular mechanism of its neuroprotective activity has been determined. The current studies show that ladostigil significantly decreased apoptosis via inhibition of the cleavage and prevention of caspase-3 activation through a mechanism related to regulation of the Bcl-2 family proteins, resulting in reduced levels of Bad and Bax and induced levels of Bcl-2. In addition, ladostigil elevated the levels of pPKC(pan). We have also followed the regulation of APP processing and found that ladostigil markedly decreased apoptotic-induced levels of holo-APP, as well as stimulated the release of the non-amyloidogenic soluble APP (sAPPalpha) into the conditioned medium via a established protein kinsae C-MAPkinase dependent pathway. Similar to ladostigil, its S-isomer, TV3279, which is a ChE inhibitor lacking MAO inhibitory activity, exerted similar neuroprotective properties and APP processing, suggesting that the mode of action is independent of MAO inhibition. These effects were shown to reside in the propargylamine moiety. These findings indicate that the dual actions of the anti-apoptotic-neuroprotective activity and the ability to modulate APP processing, could make ladostigil a potentially valuable drug for the treatment of Alzheimer's disease.
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PMID:Implications of co-morbidity for etiology and treatment of neurodegenerative diseases with multifunctional neuroprotective-neurorescue drugs; ladostigil. 1719 68

Propyl gallate is an antioxidant widely used in foods, cosmetics and pharmaceuticals. The occurrence and fate of additives in the aquatic environment is an emerging issue in environmental chemistry. To date, there is little available information about the adverse effects of propyl gallate on aquatic organisms. Therefore, the toxic effects were investigated, using five model systems from four trophic levels. The most sensitive system was the hepatoma fish cell line PLHC-1 according to total protein content, with an EC(50) of 10 microM and a NOAEL of 1 microM at 72 h, followed by the immobilization of Daphnia magna, the inhibition of bioluminescence of Vibrio fischeri, the salmonid fish cell line RTG-2 and the inhibition of the growth of Chlorella vulgaris. Although protein content, neutral red uptake, methylthiazol metabolization and acetylcholinesterase activity were reduced in PLHC-1 cells, stimulations were observed for lysosomal function, succinate dehydrogenase, glucose-6-phosphate dehydrogenase and ethoxyresorufin-O-deethylase activities. No changes were observed in metallothionein levels. The main morphological observations were the loss of cells and the induction of cell death mainly by necrosis but also by apoptosis. The protective and toxic effects of propyl gallate were evaluated. General antioxidants and calcium chelators did not modify the toxicity of propyl gallate, but an iron-dependent lipid peroxidation inhibitor gave 22% protection. The results also suggest that propyl gallate cytotoxicity is dependent on glutathione levels, which were modulated by malic acid diethyl ester and 2-oxothiazolidine-4-carboxylic acid. According to the results, propyl gallate should be classified as toxic to aquatic organisms.
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PMID:Ecotoxicological effects of the antioxidant additive propyl gallate in five aquatic systems. 1738 89

Phenserine, a derivative of physostigmine, was first described as an inhibitor of acetylcholinesterase (AChE) and was shown to improve cognition in various experimental paradigms in rodents and dogs. It was clinically tested for Alzheimer's disease, with moderate success in initial Phase II studies. Phenserine deserves attention for an additional quality of action: in addition to inhibiting AChE, it modulates the amount of beta-amyloid precursor protein (APP) in neuronal cell culture by reducing APP translation. This effect probably involves interaction of phenserine with a regulatory element in the 5'-untranslated region of the APP gene that controls APP expression. Phenserine apparently reduces translational efficiency of APP mRNA into protein, a process that may involve an interaction with iron and/or an iron-responsive element. As a consequence, phenserine reduces beta-amyloid peptide (Abeta) formation in vitro and in vivo. Phenserine is also unique because of differing actions of its enantiomers: (-)-phenserine is the active enantiomer for inhibition of AChE, whereas (+)-phenserine ('posiphen') has weak activity as an AChE inhibitor and can be dosed much higher. Both enantiomers are equipotent in downregulating APP expression. (+)-Posiphen may be a promising drug, either alone or in combination with (-)-phenserine, to attenuate the progression of Alzheimer's disease.
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PMID:Phenserine. 1759 92

Indium nitrate is mainly used as a semiconductor in batteries, for plating and other chemical and medical applications. There is a lack of available information about the adverse effects of indium compounds on aquatic organisms. Therefore, the toxic effects on systems from four trophic levels of the aquatic ecosystem were investigated. Firstly, the bacterium Vibrio fischeri, the alga Chlorella vulgaris and the cladoceran Daphnia magna were used in the toxicological evaluation of indium nitrate. The most sensitive model was V. fischeri, with a NOAEL of 0.02 and an EC(50) of 0.04 mM at 15 min. Although indium nitrate should be classified as harmful to aquatic organisms, it is not expected to represent acute risk to the aquatic biota. Secondly, PLHC-1 fish cell line was employed to investigate the effects and mechanisms of toxicity. Although protein content, neutral red uptake, methylthiazol metabolization, lysosomal function and acetylcholinesterase activity were reduced in cells, stimulations were observed for metallothionein levels and succinate dehydrogenase and glucose-6-phosphate dehydrogenase activities. No changes were observed in ethoxyresorufin-O-deethylase activity. To clarify the main events in PLHC-1 cell death induced by indium nitrate, nine modulators were applied. They were related to oxidative stress (alpha-tocopherol succinate, mannitol and sodium benzoate), disruption of calcium homeostasis (BAPTA-AM and EGTA), thiol protection (1,4-dithiotreitol), iron chelation (deferoxiamine) or regulation of glutathione levels (2-oxothiazolidine-4-carboxylic acid and malic acid diethyl ester). The main morphological alterations were hydropic degeneration and loss of cells. At least, in partly, toxicity seems to be mediated by oxidative stress, and particularly by NADPH-dependent lipid peroxidation.
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PMID:Toxicological assessment of indium nitrate on aquatic organisms and investigation of the effects on the PLHC-1 fish cell line. 1780 41

In order to study the metabolic profile of ostriches in relation to diet, 40 animals of both sexes were divided equally into two groups and fed two diets ad libitum consisting, on a dry matter basis, of the same commercial concentrate (60%) for the two groups and of corn silage (group A) or alfalfa hay (group B). In the morning, after about 12 h of fasting, blood was collected from the wing vein. The following haematological parameters were determined with an automatic system (Ektachem 250 analyser, Kodak): glucose, cholesterol, triglycerides, lactate (LAC), total protein (TP), uric acid, total bilirubin (Tbil), creatinine (CREA), calcium (Ca), magnesium (Mg), phosphorus (P), sodium (Na), potassium (K), chloride (Cl-), iron (Fe), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), cholinesterase (ChE), alpha-amylase (Amyl), lipase (LIP) and gamma-glutamyltrasferase (GGT). Diet significantly affected some parameters of the metabolic profile. Indeed, owing to the presence of alfalfa hay in the diet, group B showed, in comparison to group A, significantly higher values of uric acid (222.5 vs 387.5 mmol/L, p < 0.01), GGT (8.50 vs 11.3 U/L, p < 0.05), Tbil (8.50 vs 10.7 mmol/L, p < 0.05), Ca (2.41 vs 2.83 micromol/L, p < 0.01), Mg (1.01 vs 1.18 micromol/L, p < 0.05) and K (2.71 vs 3.16 micromol/L, p < 0.01). The levels of creatinine (27.3 vs 32.6 mmol/L, p < 0.05) and AST (344.9 vs 461.4 U/l, p < 0.01) were also higher for group B.
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PMID:Effect of diet on the metabolic profile of ostriches (Struthio camelus var. domesticus). 1784 21

Oximes are a class of compounds normally used to reverse the acetylcholinesterase (AChE) inhibition caused by organophosphates (OPs). Conversely, researches focusing on the possible antioxidant properties of these compounds are lacking in the literature. The aim of this study was to investigate the potential antioxidant and toxic properties of 3-(phenylhydrazono) butan-2-one oxime in mice. In vitro, hydrogen peroxide-induced lipid peroxidation was decreased by low concentrations of the oxime (0.1-1.0 microM); (P < 0.05). Similarly, lipoperoxidation induced by malonate and iron (Fe2+) was significantly decreased by the oxime (0.4-1.0 microM) (P < 0.05). Oxime pre-treatment did not modify the basal peroxidation level nor prevented the induced lipid peroxidation determined ex-vivo. The present results suggest that 3-(phenylhydrazono) butan-2-one oxime could be a good antioxidant compound. The absence of toxicity signs after in vivo administration of 3-(phenylhydrazono) butan-2-one oxime to mice may indicate that it could be a safe drug for further studies.
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PMID:Antioxidant properties of oxime 3-(phenylhydrazono) butan-2-one. 1850 54

Oximes are compounds generally used to reverse the acetylcholinesterase (AChE) inhibition caused by organophosphates (OPs). The aim of this study was to examine the capacity of the butane-2,3-dionethiosemicarbazone oxime to scavenge different forms of reactive species (RS) in vitro, as well as counteract their formation. The potential antioxidant and toxic activity of the oxime was assayed both in vitro and ex vivo. The obtained results indicate a significant hydrogen peroxide (H2O2), nitric oxide (NO) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity at 0.275, 0.5 and 5microM of oxime, respectively (p< or =0.05). The oxime exhibited a powerful inhibitory effect on dihydroxybenzoate formation (25microM) (p< or =0.05) and also decreased deoxyribose degradation induced by Fe2+ and via Fenton reaction (0.44 and 0.66mM, respectively) (p< or =0.05). The oxime showed a significant inhibitory effect on sigma-phenantroline reaction with Fe2+ (0.4mM) suggesting a possible interaction between the oxime and iron. A significant decrease in the basal and pro-oxidant-induced lipid peroxidation in brain, liver, and kidney of mice was observed both in vitro and ex vivo (p< or =0.05). In addition, in our ex vivo experiments the oxime did not depict any significant changes in thiol levels of liver, kidney and brain as well as did not modify the delta-aminolevulinate dehydratase (delta-ALA-D) activity in these tissues. Taken together our results indicate an in vitro and ex vivo antioxidant activity of the oxime possibly due to its scavenging activity toward different RS and a significant iron interaction.
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PMID:Butane-2,3-dionethiosemicarbazone: an oxime with antioxidant properties. 1895 Jun 8

Alzheimer's disease (AD) is a progressive degenerative disorder of the brain characterized by a slow, progressive decline in cognitive function and behavior. As the disease advances, persons have a tough time with daily tasks like using the phone, cooking, handling money or driving the car. AD affects 15 million people worldwide and it has been estimated that AD affects 4.5 million Americans. Tacrine is a reversible cholinesterase inhibitor used for treating mild to moderate AD. In the present study, an attempt was made to target the anti-Alzheimer's drug tacrine in the brain by using magnetic chitosan microparticles. The magnetic chitosan microparticles were prepared by emulsion cross-linking. The formulated microparticles were characterized for process yield, drug loading capacity, particle size, in vitro release, release kinetics and magnetite content. The particle size was analyzed by scanning electron microscope. The magnetite content of the microparticles was determined by atomic absorption spectroscopy. For animal testing, the microparticles were injected intravenously after keeping a suitable magnet at the target region. The concentrations of tacrine at the target and non-target organs were analyzed by HPLC. The magnetic chitosan microparticles significantly increased the concentration of tacrine in the brain in comparison with the free drug.
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PMID:Significant delivery of tacrine into the brain using magnetic chitosan microparticles for treating Alzheimer's disease. 1904 70


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