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)

This paper reviews chemical models of epilepsy and their relevance in the identification and characterization of anticonvulsants. For each convulsant we discuss possible modes of administration, clinical type(s) of seizures induced, proposed mechanism(s) of epileptogenesis and, where available, responsiveness of the induced seizures to anticonvulsants. The following compounds are reviewed: pentylenetetrazol, bicuculline, penicillin, picrotoxin, beta-carbolines, 3-mercaptopropionic acid, hydrazides, allylglycine; the glycine antagonist strychnine; gamma-hydroxybutyrate; excitatory amino acids (glutamate, aspartate, N-methyl-D-aspartate, quisqualate, kainate, quinolinic acid); monosubstituted guanidino compounds, metals (alumina, cobalt, zinc, iron); neuropeptides (opioid peptides, corticotropin releasing factor, somatostatin, vasopressin); cholinergic agents (acetylcholine, acetylcholinesterase inhibitors, pilocarpine); tetanus toxin; flurothyl; folates; homocysteine and colchicine. Although there are a multitude of chemical models of epilepsy, only a limited number are applied in the routine screening of potential anticonvulsants. Some chemical models have a predictive value with regard to the clinical profile of efficacy of the tested anticonvulsants. Some chemical models may contribute to a better understanding of possible mechanisms of epileptogenesis.
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PMID:Chemical models of epilepsy with some reference to their applicability in the development of anticonvulsants. 139 44

A daily dose of 1 mg/kg and 10 mg/kg of methylmercury chloride (MMC) was injected to separate sets of rats for 2 days, 7 days, and 15 days. Low and high doses of four MMC antagonists, namely N-acetyl-DL-homocysteine thiolactone (NAHT), glutathione (GSH), D-penicillamine (DPA), and sodium selenite (SEL) were injected intramuscularly (i.m.) to MMC-treated animals after an interval of half an hour. The animals were sacrificed on the 3rd, 8th, and 16th day, respectively. An additional group of rats was treated with MMC for 7 days; thereafter, it was kept free of toxic exposure for 7 days and sacrificed on the 15th day. The brain was dissected and separated into olfactory bulbs, cerebral hemispheres, cerebellum, and medulla oblongata. Each part of the central nervous system (CNS) was studied separately. We found a dose- and duration-related acetylcholinesterase (AChE) inhibition in all CNS areas. The use of antagonists showed different effects in different CNS areas, but no appreciable recovery of AChE activity could be obtained with the doses used.
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PMID:Acetylcholinesterase fluctuations in central nervous system of rat during methylmercury intoxication and chelation therapy. 818 68

Clinical trials and independent reviews support the use of cholinesterase inhibitors for treating the symptoms of patients with mild to moderate Alzheimer's disease (AD). Before initiating cholinesterase inhibitor therapy, patients should be thoroughly assessed, and the diagnosis confirmed, preferably by a specialist. Compliance with cholinesterase inhibitor therapy should be monitored and the response (in global, cognitive, functional and behavioural domains) reassessed after 2-3 months of treatment. Vitamin E may be protective against AD, and therapy with 1000 IU twice daily may be considered. There is insufficient evidence to support the use of other antioxidant agents, anti-inflammatory agents, monoamine oxidase B inhibitors, folate/homocysteine or antihypertensive drugs in patients with AD, or hormone replacement therapy in affected women.
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PMID:Pharmacological treatment of cognitive deficits in Alzheimer's disease. 1199 69

In the present work we investigated the in vitro effects of homocysteine (Hcy) and methionine (Met), metabolites accumulated in homocystinuria, on butyrylcholinesterase (BuChE) activity in rat serum. We also studied the kinetics of the inhibition of BuChE activity caused by Hcy. For determination of BuChE we used serum of 60-day-old Wistar rats, which was incubated in the absence (control) or presence of Hcy (0.01-0.5 mM) or Met (0.2-2.0 mM). The kinetics of the interaction of Hcy and BuChE was determined using the Lineweaver-Burk double reciprocal plot. Results showed that serum BuChE activity was not altered by Met, but it was significantly inhibited (37%) by 500 microM Hcy, a concentration similar to those found in blood of homocystinuric patients. The apparent Km values, in the absence and presence of 500 microM of Hcy, were 0.034 and 0.142 mM, respectively, and V(max) of BuChE for acetylcholine (ACh) as substrate was 1.25 micromol ACSCh/h/mg of protein. The Ki value obtained was 120 microM, and the inhibition was of the competitive type, suggesting a common binding site for Hcy and ACh. It is proposed that inhibition of cholinesterase activity may be one of the mechanisms involved in the neurological dysfunction observed in homocystinuria.
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PMID:Homocysteine inhibits butyrylcholinesterase activity in rat serum. 1456 69

Coronary artery ectasia (CAE) is well-recognized, angiographic finding of abnormal coronary dilatation, and detected in 0.3-5.3% of angiographic studies. The gold standard for diagnosis this type of aneurysm is coronary angiography, which provides information about the size, sample, location and number of aneurysms. Despite growing prevalence in recent years, controversy still exists as to the pathogenetic mechanisms that underlie this entity. An increased incidence of CAE has been reported in several disorders. Examples include atherosclerotic vascular disease, heterozygous familial hypercholesterolemia, usage of substances including herbicide spray, acetylcholinesterase inhibitors and nitrates, previous arterial balloon angioplasty, polyarteritis nodosa and Kawasaki syndrome. In addition, possible factors contributing to CAE are imbalance between matrix metalloproteinase and tissue inhibitor of metalloproteinase, angiotensin converting enzyme genotype, elevated homocysteine levels, cocaine user, smoking, vascular trauma, nitrate use and diabetes. Emerging investigations have pinpointed inflammation as a central process in all stages of atherosclerosis. This inflammatory process culminates in acute thrombotic complications and clinical events, which is involved in different clinical settings of atherosclerotic diseases. Recent data have also showed that CAE is associated with inflammatory response presented as elevated inflammatory cytokines and C-reactive protein. Accordingly, more complete understanding of the pro- and anti-inflammatory circuits that operate during CAE in particular may foster the development of novel therapeutic approaches.
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PMID:Is any link between inflammation and coronary artery ectasia? 1722 19

Current treatments for Alzheimer's disease involve inhibiting cholinesterases. Conversely, cholinesterase stimulation may be deleterious. Homocysteine is a known risk factor for Alzheimer's and vascular diseases and its active metabolite, homocysteine thiolactone, stimulates butyrylcholinesterase. Considering the opposing effects on butyrylcholinesterase of homocysteine thiolactone and cholinesterase inhibitors, understanding how these molecules alter this enzyme may provide new insights in the management of dementia. Butyrylcholinesterase does not strictly adhere to Michaelis-Menten parameters since, at higher substrate concentrations, enzyme activation occurs. The substrate activation equation for butyrylcholinesterase does not describe the effects of inhibitors or non-substrate activators. To address this, global data fitting was used to generate a flexible equation based on Michaelis-Menten principles. This methodology was first tested to model complexities encountered in inhibition by imidazole of beta-galactosidase, an enzyme that obeys Michaelis-Menten kinetics. The resulting equation was sufficiently flexible to permit expansion for modeling activation or inhibition of butyrylcholinesterase, while accounting for substrate activation of this enzyme. This versatile equation suggests that both the inhibitor and non-substrate activator examined here have little effect on the substrate-activated form of butyrylcholinesterase. Given that butyrylcholinesterase inhibition can antagonize stimulation of this enzyme by homocysteine thiolactone, cholinesterase inhibition may have a role in treating Alzheimer and vascular diseases related to hyperhomocysteinemia.
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PMID:A versatile equation to describe reversible enzyme inhibition and activation kinetics: modeling beta-galactosidase and butyrylcholinesterase. 1730 93

In the present study we investigated the effect of homocysteine administration, the main metabolite accumulating in homocystinuria, on cholinesterase activity in rat and human serum. For the in vivo study, 8-, 15- and 60-day-old rats received one subcutaneous injection of homocysteine (0.3, 0.4 or 0.6 micromol/g of body weight, respectively) or saline (control) and were sacrificed 1h later, when serum was collected in order to determine cholinesterase activity. For the in vitro studies, serum of 8-, 15- and 60-day-old untreated rats or 20-25- and 52-60-day-old human beings (healthy volunteers) were incubated with 10-500 microM homocysteine. Results showed that acute hyperhomocysteinemia (in vivo study) significantly reduced cholinesterase activity in the serum of rats of all ages tested. We also observed that 500 microM homocysteine added to the incubation medium (in vitro study) significantly inhibited cholinesterase activity both in serum of rats and humans. Our findings seem to reinforce the proposed associations of cholinesterase activity with hyperhomocysteinemia.
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PMID:Homocysteine reduces cholinesterase activity in rat and human serum. 1748 43

Choline is an essential nutrient that seems to be involved in a wide variety of metabolic reactions and functions, that affect the developing brain. The aim of this study was to: (a)examine the effects of early age choline deficient diet (CDD) administration on the total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), (Na(+),K(+))-ATPase and Mg(2+)-ATPase in the rat brain, (b)investigate the effect of feeding restoration into an equilibrated diet on the above parameters, and (c)study the role of homocysteine (Hcy), L: -phenylalanine (Phe) and L: -alanine (Ala) in certain of the above effects. Male and female Wistar rats were continuously kept off choline (Ch) during their gestational period of life, as well as during the first 6 weeks of their post-gestational life. The animals were sacrificed by decapitation and their whole brains were rapidly removed and homogenated. Their enzyme activities were measured spectrophotometrically. Moreover, in vitro experiments were conducted in order to estimate the effects of Hcy (0.3 mM), Phe (1.2 mM) and/or Ala (1.2 mM) on the above parameters. The administration of CDD led to a statistically significant decrease of the rat brain TAS (-29%, p < 0.001) and to a significant increase of both AChE (+20%, p < 0.001) and (Na(+),K(+))-ATPase (+35%, p < 0.001) activities. Mg(2+)-ATPase activity was found unaltered. Equilibrated diet, administered to early age CDD-treated rats of both sexes for an additional period of 18 weeks, restored the above parameters to control levels. Moreover, the in vitro experiments showed that Hcy could simulate these changes (at least under the examined in vitro conditions), while both Phe and Ala act protectively against the CDD-induced effects on the examined rat brain enzyme activities. The effects of early age CDD-feeding on the examined parameters are proved to be reversible through restoration to equilibrated diet, while our data suggest a role for Hcy (as a causative parameter for the CDD-induced effects) and a possible protective role for Phe and Ala (in reversing the observed CDD-induced effects).
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PMID:Equilibrated diet restores the effects of early age choline-deficient feeding on rat brain antioxidant status and enzyme activities: the role of homocysteine, L-phenylalanine and L-alanine. 1864 68

Mild cognitive impairment (MCI) and cognitive impairment, no dementia (CIND) might be the optimum stage at which to intervene with preventative therapies. This article reviews recent work on the possible treatment and presents evidence-based recommendations approved at the meeting of the Third Consensus Conference on the Diagnosis and Treatment of Dementia held in Montreal in March, 2006. A number of promising nonpharmacologic interventions have been examined. Associations exist with both cognitive and physical activity that suggest that both of these, together or separately, can delay progression to dementia. Similarly, case control studies as well as prospective long-term studies suggest a number of low toxicity interventions and supplements that might significantly impact on MCI progression; folate, B(6), and B(12) to lower homocysteine levels, omega-fatty acids, and anti-oxidants (fruit juices or red wine) are good examples. In selected genotypes such as individuals with APOE e4, therapy with donepezil might slow progression. The concern, however, is that none of these therapies (including cholinesterase inhibitors) have demonstrated a clinically meaningful effect with randomized, placebo-controlled studies. Just as randomized controlled studies have failed to support primary prevention of dementia by using estrogen or nonsteroidal anti-inflammatory drugs (NSAIDs), there exists the possibility that well-designed randomized controlled trials might fail to definitively demonstrate putative or promising mild cognitive impairment interventions. Pharmacologic interventions and nonpharmacologic therapies, while tantalizing, are currently for the most part insufficiently proven to allow serious consideration by physicians. Recommendation were supported for a general "healthy lifestyle" including physical exercise, healthy nutrition, smoking cessation, and mental stimulation. Close monitoring and treatment of vascular risk factors are justified and were also supported.
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PMID:Mild cognitive impairment and cognitive impairment, no dementia: Part B, therapy. 1959 49

Our aim was to perform a preliminary study of blood flow in the peripheral microcirculation in patients with heart failure. Cardiac patients were investigated to establish possible microcirculatory changes due to this pathology. We evaluated 16 patients (non-smokers, dislipidemic with hypercholesterolemia), receiving oral treatment and in NYHA class 2.3 +/- 0.5. A dilated cardiomyopathy (DCM) group was evaluated before cardiac resynchronization therapy (CRT) obtained by biventricular intra-cardiac defibrillator (ICD) implantation, and again 3 months after its implantation. We measured the ejection fraction (EF), peripheral blood flow (using laser Doppler) at the left wrist on the volar side, capillary morphology (using computerized videocapillaroscopy) on the nail bed of the 4th finger of the left hand, rheological status (using the LORCA), as well as hematocrit, hemoglobin concentration, red blood cell (RBC) surface acetylcholinesterase (AchE), and homocysteine. Our data show that in the DCM vs. control group, peripheral flow did not depend only on the heart: throughout the study, blood flow did not change significantly compared to controls and was increased after CRT. There was no decrease in aggregation time. The blood flow did not alter RBC deformability or RBC surface AchE. Due to the lower oxygenation and to a non-significant increase in the number of capillaries after CRT, DCM patients are at higher cardiovascular risk than healthy subjects.
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PMID:Could dilated cardiomyopathy alter the peripheral microcirculation and blood rheology? 2020 69


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