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:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aflatoxin (AF)-contaminated and fumonisin B1 (FB1)-contaminated (culture material from Fusarium moniliforme) diets were fed singly and in combination to growing cross-bred barrows. Six barrows (3 replicates of 2 each; mean body weight, 17.5 kg) per group were fed: 0 mg of AF and 0 mg of FB1/kg of feed (control); 2.5 mg of AF/kg of feed; 100 mg of FB1/kg of feed; or 2.5 mg of AF plus 100 mg of FB1/kg of feed for 35 days. The effects on production performance, serum biochemical, hematologic, immunologic, and pathologic measurements were evaluated. Body weight, gain, and feed consumption were significantly (P < 0.05) decreased by AF and AF plus FB1 diets. The FB1 diet decreased feed consumption, and although body weight was numerically decreased, it was not statistically significant. Aflatoxin increased serum gamma-glutamyltransferase (GGT) activity and total iron concentration and decreased urea nitrogen concentration and unsaturated iron-binding capacity. The FB1-alone diet increased serum GGT activity, whereas the AF plus FB1 diet increased serum aspartate transaminase, cholinesterase, alkaline phosphatase, and GGT activities, increased RBC count, triglycerides, and total iron concentrations, and decreased unsaturated iron-binding capacity and urea nitrogen concentration. For the most part, the effects of the AF plus FB1 diet on body weight and hematologic measurements could be considered additive. However, the effect of the AF plus FB1 diet on cholinesterase and alkaline phosphatase activities was greater than additive and was a synergistic response. One pig in the FB1-diet group and 2 pigs in the combination-diet group died. Postmortem lesions in pigs of the FB1-diet group consisted of ascites and increased liver weight. Observations at necropsy for pigs of the AF plus FB1-diet group consisted of hydrothorax, ascites, pulmonary edema, gastric erosions and ulceration, and increased liver and spleen weights. The AF diet increased relative liver weight and resulted in liver that was pale, rubbery, and resistant to cutting. Histologic lesions consisted of hepatic necrosis or degeneration, or both, with variable degrees of bile duct proliferation in barrows of the AF-diet groups. Renal tubular nephrosis was observed in barrows of the FB1-diet group, but this was not consistent in the AF plus FB1-diet group. Cell-mediated immunity, as measured by mitogen-induced lymphoblastogenic stimulation index, was decreased in barrows of the AF and FB1-diet groups, and values in barrows given the combination diet were significantly decreased from those in barrows given the single toxin diets. It was concluded that AF and FB1 (from culture material), singly or in combination, can adversely affect clinical performance, serum biochemical, hematologic, and immunologic values and induce lesions in growing barrows. For most of the variables we evaluated under our study conditions and dosages of toxins, measurements were affected more by the combination diet than by either single toxin diet, and the toxic responses could be described as additive or more than additive, particularly for induction of liver disease.
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PMID:Influence of aflatoxin and fumonisin B1-containing culture material on growing barrows. 859 31

The aim of this prospective study was to evaluate if there was a statistical correlation between allogeneic blood transfusion and postoperative infections, and if this could have a dose-dependent pattern. The evaluation was based on multiple logistic and receiver operating characteristics (ROC) curve analyses. On hospital admission the following parameters were determined in 267 consecutive patients with colorectal cancer: hemoglobin, serum albumin, serum cholinesterase activity, total iron binding capacity and weight loss. Duration of operation, operative blood loss, amount of transfused blood, Dukes' cancer stage and occurrence of postoperative infections were also recorded. One hundred and thirty-two patients (49.4%) were given perioperatively allogeneic blood. Postoperative infections developed in 47 (17.6%) patients. Multivariate analysis identified allogeneic blood transfusion as the only variable related to the occurrence of postoperative infections (p < 0.05). ROC curve analysis showed that the risk for the occurrence of infection was significantly higher in patients transfused one unit of blood (p < 0.01). Moreover, a significant trend between increasing number of transfused blood units and susceptibility to infection was found (p < 0.00019).
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PMID:A single unit of transfused allogeneic blood increases postoperative infections. 891 60

Concentrations of 34 biochemical constituents of sera were determined on 998 randomly selected urban school children and adolescents aged 8-18 years from Zagreb, Croatia. Reference intervals were obtained by using non-parametric methods to estimate 2.5 and 97.5 percentiles of distribution as upper and lower normal reference intervals, according to the IFCC recommendations. These were compared to reference intervals in the healthy adult population, aged 20-30 years from the same geographical area. Serum glucose, potassium, sodium, chloride, magnesium, iron, zinc, total serum proteins and electrophoretic fractions, and amylase, did not show age or sex differences; total serum bilirubin, total calcium, phosphate, high density lipoprotein cholesterol, total iron binding capacity, unsaturated iron binding capacity, copper, aspartate aminotransferase, alkaline phosphatase, cholinesterase, creatine kinase, and lactate dehydrogenase had higher reference intervals than the adult population. Urea, creatinine, urate, alanine aminotransferase, gamma-glutamyltransferase, total cholesterol and low density lipoprotein-cholesterol, and triglycerides had lower reference intervals than the adult population.
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PMID:Pediatric reference intervals for 34 biochemical analytes in urban school children and adolescents. 967 91

Tacrine (1,2,3,4-tetrahydro-9-aminoacridine), a reversible cholinesterase inhibitor, was effective in the treatment of Alzheimer's disease (AD). In turn, desferrioxamine (DFO), a chelating agent with ability to chelate iron and aluminum (Al), produced a 50% decrease in the rate of cognitive decline in patients with AD. Since combined therapy with tacrine and DFO might be more effective than individual administration of these drugs for the treatment of AD patients, this study evaluated the toxic effects of concomitant administration of tacrine and DFO to rats. Three groups of 8 rats each received the following treatments for 8 w: 80 mg DFO/kg/d i.m., 7.5 mg tacrine/kg/d po, or 80 mg DFO/kg/d i.m. +7.5 mg tacrine/kg/d po. A control group received distilled water by gavage daily and a 0.9% saline injection i.m. The administration of DFO + tacrine for 8 w did not increase most of the side effects caused by the individual DFO or tacrine administrations. These results open the possibility of considering the effectiveness of simultaneous administration of DFO and tacrine as a palliative treatment for AD patients.
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PMID:Effects of simultaneous administration of desferrioxamine and tacrine in rats. 977 61

Oral exposure to chlorpyrifos (CHP) in the rat results in an initial hypothermic response followed by a delayed fever. Fever from infection is mediated by the release of cytokines, including interleukin-6 (IL-6) and tumor necrosis factor (TNF alpha). This study determined if the CHP-induced fever involves cytokine-mediated mechanisms similar to that of infectious fevers. Long-Evans rats were gavaged with the corn oil vehicle or CHP (10-50 mg/kg). The rats were euthanized and blood collected at various times that corresponded with the hypothermic and febrile effects of CHP. Plasma IL-6, TNF alpha, cholinesterase activity (ChE), total iron, unsaturated iron binding capacity (UIBC), and zinc were measured. ChE activity was reduced by approximately 50% 4 h after CHP. There was no effect of CHP on IL-6 when measured during the period of CHP-induced hypothermia or fever. TNF alpha levels nearly doubled in female rats 48 h after 25 mg/kg CHP. The changes in plasma cytokine levels following CHP were relatively small when compared to > 1000-fold increase in IL-6 and > 10-fold rise in TNF alpha following lipopolysaccharide (E. coli; 50 microg/kg; i.p.)-induced fever. This does not preclude a role of cytokines in CHP-induced fever. Nonetheless, the data suggest that the delayed fever from CHP is unique, involving mechanisms other than TNF alpha and IL-6 release into the circulation characteristic of infectious fevers.
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PMID:Are circulating cytokines interleukin-6 and tumor necrosis factor alpha involved in chlorpyrifos-induced fever? 1041 84

Machine autotransfusion using cell-saver is a well-established method of saving homologous blood during extensive surgical procedures. The processing of blood may induce the initiation of lipid peroxidation (LPO) with the release of hepatotoxic products. A series of 42 patients undergoing primary (n = 20) or revision (n = 22) hip arthroplasty comprised the study group. Patients received an average of 1,260 ml of autologous blood and 2.2 units of homologous packed cells. The concentration of thiobarbituric acid reactive substances (TBARS) as LPO metabolites was measured in the patients' plasma, in the autologous packed cells as well as in the supernatants of the cell-saver-processed blood. Additionally, parameters of iron metabolism, haemoglobin levels, haematocrit as well as the activities of so-called liver enzymes aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidase and cholinesterase were determined. An initiation of LPO was detectable during the process of machine autotransfusion, but this took place mainly ex vivo. High concentrations of TBARS were detectable in the supernatants after cell-separation processing. We observed a decline in haemoglobin concentration and haematocrit during the perioperative period. Postoperatively, we found a significant iron deficiency as a consequence of the perioperative blood loss. There was not sufficient evidence of a postoperative liver disorder induced by toxic metabolites of LPO. To sum up, there is only a low contamination of the organism with LPO products during the process of machine autotransfusion. Therefore, an induction of liver damage seems to be improbable.
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PMID:[Initiation of lipid peroxidation (LPO) in blood during intraoperative mechanical autotransfusion--is hepatotoxicity of lipid peroxidation products of clinical significance?]. 1081 96

The reduction in levels of the potentially toxic amyloid-beta peptide (Abeta) has emerged as one of the most important therapeutic goals in Alzheimer's disease. Key targets for this goal are factors that affect the expression and processing of the Abeta precursor protein (betaAPP). Earlier reports from our laboratory have shown that a novel cholinesterase inhibitor, phenserine, reduces betaAPP levels in vivo. Herein, we studied the mechanism of phenserine's actions to define the regulatory elements in betaAPP processing. Phenserine treatment resulted in decreased secretion of soluble betaAPP and Abeta into the conditioned media of human neuroblastoma cells without cellular toxicity. The regulation of betaAPP protein expression by phenserine was posttranscriptional as it suppressed betaAPP protein expression without altering betaAPP mRNA levels. However, phenserine's action was neither mediated through classical receptor signaling pathways, involving extracellular signal-regulated kinase or phosphatidylinositol 3-kinase activation, nor was it associated with the anticholinesterase activity of the drug. Furthermore, phenserine reduced expression of a chloramphenicol acetyltransferase reporter fused to the 5'-mRNA leader sequence of betaAPP without altering expression of a control chloramphenicol acetyltransferase reporter. These studies suggest that phenserine reduces Abeta levels by regulating betaAPP translation via the recently described iron regulatory element in the 5'-untranslated region of betaAPP mRNA, which has been shown previously to be up-regulated in the presence of interleukin-1. This study identifies an approach for the regulation of betaAPP expression that can result in a substantial reduction in the level of Abeta.
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PMID:Phenserine regulates translation of beta -amyloid precursor protein mRNA by a putative interleukin-1 responsive element, a target for drug development. 1140 70

The prevalence of anemia increases with age and is frequently multifactorial. We postulated that malnutrition contributes to anemia in the elderly and is underdiagnosed. Our objective was to analyze the prevalence of anemia and its association with nutritional status in a hospitalized geriatric population. Included in this retrospective cohort study were 186 consecutive patients admitted in 1997 to a geriatric unit of a university hospital. We compared hematological and chemical blood tests routinely performed upon admission in patients with anemia (hemoglobin <120 g/l) and without anemia (hemoglobin > or = 120 g/l). Using these admission parameters, we defined a multiparameter score of malnutrition by low lymphocyte counts, decreased values of albumin, cholesterol, transferrin, cholinesterase, and zinc, iron deficiency by low transferrin saturation and normal C-reactive protein, and inflammation by increased C-reactive protein and high transferrin saturation. Of the 186 patients, 82 (44%) met the criteria for anemia on admission. In univariate analysis, patients with anemia differed significantly from patients with normal hemoglobin exhibiting lower serum values of albumin, iron, transferrin, cholesterol, cholinesterase, zinc, transferrin saturation, and lymphocyte count and higher C-reactive protein levels. Using a multiparameter score, anemia correlated significantly with parameters of malnutrition (P=0.0001) but not with iron deficiency (P=0.5) or with inflammation (P=0.08). In a multivariate logistic regression model, anemia was significantly associated with serum albumin (RR: 1.138; 95% CI: 1.056-1.227; P=0.0007), cholinesterase (RR: 1.387; 95% CI 1.122-1.714; P=0.0025), and transferrin saturation (RR: 1.05; 95% CI: 1.012-1.09; P=0.009). We conclude that malnutrition may play an important etiologic role in anemia in the elderly.
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PMID:Anemia: an indicator for malnutrition in the elderly. 1144 33

Hut and village-scale trials with solid and liquid-type dichlorvos dispensers were carried out in 1961 in the vicinity of Lagos, Nigeria, by the WHO Insecticide Testing Unit. Bioassay results indicated that with a single application satisfactory mortalities of caged mosquitos could be obtained for a period of 12-13 weeks in mud-walled huts, whether with galvanized corrugated-iron roofs or with thatched roofs. Chemical analysis of air samples showed that satisfactory concentrations of dichlorvos vapour were maintained throughout the huts for about 12 weeks, after which time sublethal concentrations were observed first near the floors of the dwellings. No depression in blood or plasma cholinesterase was noted in the exposed inhabitants
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PMID:A VILLAGE-SCALE TRIAL WITH DICHLORVOS AS A RESIDUAL FUMIGANT INSECTICIDE IN SOUTHERN NIGERIA. 1405 80

Degeneration of nigrostriatal dopamine neurons and cholinergic cortical neurones are the main pathological features of Parkinson's disease (PD) and for the cognitive deficit in dementia of the Alzheimer' type (AD) and in dementia with Lewy bodies (DLB), respectively. Many PD and DLB subjects have dementia and depression resulting from possible degeneration of cholinergic and noradrenergic and serotonergic neurons. On the other hand, AD patients may also develop extrapyramidal features as well as depression. In both PD and AD there is, respectively, accumulation of iron within the melanin containing dopamine neurons of pars compacta and with in the plaques and tangle. It has been suggested that iron accumulation may contribute to the oxidative stress induced apoptosis reported in both diseases. This may result from increased glia hydrogen peroxide producing monoamine oxidase (MAO) activity that can generate of reactive hydroxyl radical formed from interaction of iron and hydrogen peroxide. We have therefore prepared a series of novel bifunctional drugs from the neuroprotective-antiapoptotic antiparkinson monoamine oxidase B inhibitor, rasagiline, by introducing a carbamate cholinesterase (ChE) inhibitory moiety into it. Ladostigil (TV-3326, N-propargyl-3R-aminoindan-5yl)-ethyl methylcarbamate), has both ChE and MAO-AB inhibitory activity, as potential treatment of AD and DLB or PD subjects with dementia Being a brain selective MAO-AB inhibitor it has limited potentiation of the pressor response to oral tyramine and exhibits antidepressant activity similar to classical non-selective MAO inhibitor antidepressants by increasing brain serotonin and noradrenaline. Ladostigil inhibits brain acetyl and butyrylcholinesterase in rats and antagonizes scopolamine-induced inhibition of spatial learning. Ladostigil like MAO-B inhibitor it prevents MPTP Parkinsonism in mice model and retains the in vitro and in vivo neuroprotective activity of rasagiline. Ladostigil, rasagiline and other propargylamines have been demonstrated to have neuroprotective activity in several in vitro and in vivo models, which have been shown be associated with propargylamines moiety, since propargylamines itself possess these properties. The mechanism of neuroprotective activity has been attributed to the ability of propargylamines-inducing the antiapoptotic family proteins Bcl-2 and Bcl-xl, while decreasing Bad and Bax and preventing opening of mitochondrial permeability transition pore. Iron accumulates in brain regions associated with neurodegenerative diseases of PD, AD, amyotrophic lateral sclerosis and Huntington disease. It is thought to be involved in Fenton chemistry oxidative stress observed in these diseases. The neuroprotective activity of propargylamines led us to develop several novel bifunctional iron chelator from our prototype brain permeable iron chelators, VK-28, possessing propargylamine moiety (HLA-20, M30 and M30A) to iron out iron from the brain. These compounds have been shown to have iron chelating and monoamine oxidase A and B selective brain inhibitory and neuroprotective-antiapoptotic actions.
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PMID:Bifunctional drug derivatives of MAO-B inhibitor rasagiline and iron chelator VK-28 as a more effective approach to treatment of brain ageing and ageing neurodegenerative diseases. 1562 Dec 13


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