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)

E2020 is a new cholinesterase inhibitor with a novel chemical structure, which is under clinical investigation for use in Alzheimer's disease in Japan and the USA. Three separate studies were conducted to evaluate the safety and to establish the pharmacokinetic profile of E2020 after oral administration to healthy male subjects. E2020 was administered as: (1) single oral doses (0.3 mg, 1 mg, 2 mg, 5 mg, 8 mg and 10 mg) in a fasting condition, (2) a single oral dose (2 mg) after a meal and (3) repeated oral doses (2 mg once daily for 21 days). The concentrations of E2020 and its metabolites in plasma, serum, urine and feces were determined by HPLC methods with UV detection. E2020 was generally well tolerated by all subjects. In the single-dose study, there was a linear relationship between dose and mean AUC. The mean plasma half-life was about 50 hours and was dose-independent. The total clearance and renal clearance of E2020 were also dose-independent and the mean values after 10 mg dosing were 9.7 l/hour and 0.86 l/hour, respectively. The cumulative total urinary and fecal excretion of the sum of unchanged E2020 and its metabolites at 264 hours after the administration of the single 10-mg-dose was 36.1% and 8.6% of the dose, respectively. The mean serum protein binding was 92.6%. No effect of food intake on the pharmacokinetics was observed. Evaluation of the mean trough levels and AUC0-24 of E2020 indicated that a steady-state was achieved after approximately 2 weeks of daily dosing.
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PMID:Pharmacokinetics of E2020, a new compound for Alzheimer's disease, in healthy male volunteers. 831 52

Primary sclerosing cholangitis, a chronic cholestatic liver disease, frequently leads to an impairment of liver function. In nine men and two women, aged 23 to 57 years, we prospectively studied for three to six years the effect of treatment with ursodeoxycholic acid (UDCA) on liver function. 10 mg UDCA/kg bw significantly reduced serum activities of AP, gamma GT, AST and ALT for several years. After three years of treatment, however, serum concentration of bilirubin was higher than before therapy in eight out of eleven patients (1.8 +/- 0.8 versus 0.9 +/- 0.1 mg/dl; p = 0.01). Likewise, serum concentration of bilirubin was higher in eight out of nine patients after four years of treatment (1.3 +/- 0.3 versus 0.9 +/- 0.1 mg/dl; p = 0.03). In most cases, however, the increase was discrete. Parameters of synthetic liver function (coagulation, serum protein concentration, serum activity of cholinesterase) remained constant in the observation time. Quantitative liver function tests (galactose elimination capacity and indocyanine green half-life) also showed little variation in the observation time. We conclude that UDCA treatment significantly improves serum activities of liver enzymes for several years. Nevertheless, serum bilirubin concentration, believed to be of prognostic value in patients with PSC, seems to rise slowly over time. Serial determinations of galactose elimination capacity and indocyanine green halflife are not superior to conventional liver function tests in the timing of liver transplantation in the individual patient.
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PMID:[Primary sclerosing cholangitis: conventional and quantitative liver function tests during long-term therapy with ursodeoxycholic acid]. 865 87

The disposition kinetics of fenvalerate were studied in goats after dermal application of 100 ml of 0.25% (w/v) solution. The insecticide persisted in the blood for 72 h. The mean (+/- SEM) Vd(area) and apparent t 1/2 (beta) were 9.92 +/- 1.44 L/kg and 17.51 +/- 2.65 h, while the AUC and ClB values were respectively 82.15 +/- 7.40 micrograms h/ml and 0.56 +/- 0.05 L/(kg h). Four days after the dermal application, the highest concentration of fenvalerate residues was found in the adrenal gland, followed by the biceps muscle, omental fat, liver, kidney, lung and cerebrum in that order. Fenvalerate caused hyperglycaemia but had no effect on serum protein and cholesterol levels. Serum acetylcholinesterase activities were increased after 24 h but were below the initial values from 48 to 120 h.
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PMID:The disposition kinetics and residues of fenvalerate in tissues following a single dermal application to black Bengal goats. 873 25

Thermolabile beta-2 macroglycoprotein is a novel serum protein that was detected by an autoantibody in sera of a Japanese woman with systemic lupus erythematosus. We developed an enzyme-linked immunosorbent assay for this glycoprotein and measured its serum levels in patients with chronic liver disease. There were significant correlations between serum levels of this glycoprotein and those of albumin and cholinesterase. The serum levels of TL beta 2MG decreased with increasing severity of cirrhosis. Immunohistochemical staining using monoclonal anti-thermolabile beta-2 macroglycoprotein antibody revealed positive staining in the cytoplasm of the hepatocytes. These data strongly suggested that hepatocyte may be one of the production sites of this glycoprotein. Measurement of serum levels of this glycoprotein was useful for evaluation of hepatic function in chronic liver disease.
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PMID:Thermolabile beta-2 macroglycoprotein (Hakata antigen) in liver disease: biochemical and immunohistochemical study. 893 53

52-week oral repeated-dose S-1 toxicity studies were conducted. Male and female dogs were orally treated with 0, 0.1, 0.5 or 2.5 mg/kg/day for 52 weeks and permitted to recover for 13 weeks. Furthermore, to estimate the no-toxic dose, male and female dogs were given S-1 orally for 52 weeks at doses of 0, 0.004 and 0.02 mg/kg/day. The 2.5 mg/kg/day regimen produced one dead or moribund dog of each sex; black-brown patch (melanin deposition) and inflammatory changes in the eyes and skin; decreased in body weight gains; increases in MCV, MCH, monocyte ratio, and serum protein and uric acid; decreases in lymphocyte ratio and erythrocyte count, hematocrit, hemoglobin, albumin, A/G ratio, cholesterol (esterified, total and free), phospholipids, triglycerides, cholinesterase activity and creatinine; increases in relative liver and adrenal weights. Histopathological examinations revealed melanin deposits in superficial lymph nodes, increases in macrophage and plasma cell accumulation, and corneal atrophy accompanied by melanin deposits and capillary proliferation. A slight black-brown patch (melanin deposition) in the conjunctiva and skin was observed in the 0.1 and 0.5 mg/kg/day groups. No drug-related changes were observed in groups that received 0.02 and 0.004 mg/kg/day. All changes observed during the treatment period disappeared during recovery except for melanin deposits in the conjunctiva and superficial lymph nodes, corneal opacity, and a few hematological and blood chemistry parameters. In conclusion, the no-toxic dose in these 52-week studies was estimated to be 0.02 mg/kg/day.
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PMID:[A 52-week oral toxicity study of a new antineoplastic agent S-1 in dogs]. 902 62

The serum protein designated 90K/Mac-2BP has been found at elevated concentrations in the sera of patients with various types of cancer and viral infections. The importance of the 90K/Mac-2BP serum concentrations in predicting the response towards interferon-alpha treatment for hepatitis C virus (HCV) infection prompted us to utilize a new ELISA for soluble human 90K/Mac-2BP to monitor the serum concentrations of this protein in our HCV-positive patients. Seventy HCV-PCR and anti-HCV antibody positive patients were analyzed for their serum levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, cholinesterase, HCV-viral load, viral subtypes, and 90K/Mac-2BP. On correlation of age and 90K/Mac-2BP levels, we found an apparent correlation that was proved rather to be a strong dependence of 90K/Mac-2BP concentrations on disease severity/duration, which increases with age. Multiple correlation analysis demonstrated the independent nature of 90K/Mac-2BP concentrations, underscoring the potential high utility of this new marker. Our data corroborate the potential of the scavenger receptor family protein 90K/Mac-2BP as an independent predictor of disease severity during HCV infection.
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PMID:Serum protein 90K/Mac-2BP is an independent predictor of disease severity during hepatitis C virus infection. 1090 55

We classified 1017 patients with community-acquired pneumonia requiring hospitalization experienced in Kawasaki Medical School Kawasaki Hospital during the past 15 years into five age groups (< or = 54 years old, 55-64 years old, 65-74 years old, 75-84 years old, > or = 85 years old). With particular emphasis on the elderly patients, we then compared the clinical and microbiological findings in the five groups. The results were as follows; (1) Half of patients in the over 85 years old group were bed-ridden. (2) The proportion receiving antibiotics before hospitalization decreased with age. (3) There were striking atypical pneumonic symptoms, such as dyspnea and consciousness disturbance in the two age groups over 75 years old. (4) Hypotension (shock) increased with age. (5) Markers of nutritional conditions, such as serum protein, albumin, cholinesterase, and hypoxia remarkably increased in the two age groups over 75 years old. (6) There were no significant differences in the isolation rate of etiological microorganisms. (7) The number of polymicrobial agents in the < or = 54 years old group was lower than that in the other age groups. (8) Mycoplasma pneumoniae was most significantly higher in < or = 54 years old group, Haemophilus influenzae in patients 55-64 years old, and Streptococcus pneumoniae in both 65-74 and 75-84 years old groups. (9) The isolation rate of MSSA, gram-negative bacilli such as Klebsiella pneumoniae, Pseudomonas aeruginosa, respiratory viruses increased with age. (10) The amount of sepsis increased with age. (11) The prognosis was poor in the two groups over 75 years old because the mortality rate (over 10%) was higher that for the other age groups.
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PMID:[Clinical analysis of patients with community-acquired pneumonia requiring hospitalization classified by age group]. 1132 79

The effect of exposure to sub-lethal concentrations of cypermethrin, a synthetic pyrethroid pesticide, on biochemical parameters of muscle, blood and enzyme activities in brain, liver and kidney of the Indian major carp, Labeo rohita was studied. The sub-lethal exposure studies were done for up to 45 days at 1/10 and 1/50 of 96 h LC(50) of cypermethrin. The 96 h LC(50) was found to be 0.139 ppm. RNA levels decreased while DNA levels were elevated. Acid phosphatase was unchanged while alkaline phosphatase was depleted. Brain acetylcholinesterase activity was decreased significantly (P<0.05) over a period of 45 days at both cypermethrin concentrations. Lactate dehydrogenase activity in brain and liver was elevated, but inhibited in kidney. Succinate dehydrogenase and ATPase activities were depleted in brain, kidney and liver. There was a decrease in serum protein level over control at both concentrations of the pyrethroid. Blood glucose level and total leucocytes were elevated compared with controls at either concentration from day 15 to day 45. Haemoglobin percentage and total erythrocytes decreased in both sub-lethal concentrations. Extracts of the herb Datura stramonium were effective in countering the toxicity of this pesticide. Our data suggest that sub-lethal exposure of cypermethrin alters the biochemical, haematological parameters and enzymes of organs tissue and exert stress on the fish. Plant extracts may be useful in counteracting some of these effects.
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PMID:Toxicity of cypermethrin in Labeo rohita fingerlings: biochemical, enzymatic and haematological consequences. 1252 23

This study examined the effects of oral administration of an enzymatic protein hydrolysate from green microalga Chlorella vulgaris (Cv-PH) on the nutritional recovery of malnourished Balb/c mice after a 3-day fasting period. Mice were refed with commercial diet supplemented or not supplemented with Cv-PH (500 mg/kg) for 8 days. Regardless of the diet used during refeeding, animal body weights and serum protein concentrations did not differ between groups. Mice given Cv-PH had a significant increase in hemoglobin concentrations. Most serum amino acid levels were similar in the control and Cv-PH animals. Starved mice refed with Cv-PH showed normal liver functions, as judged by liver weight, protein concentration, and the enzymatic activities of cholinesterase and arginase. Cv-PH increased DNA, protein content, and gut-mucosal weight. In addition, brush-border oligosaccharidase activities were also higher in the Cv-PH group. These findings suggest that Chlorella protein hydrolysate can be used to develop specific formulations suitable for pharmacologic nutrition.
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PMID:Oral administration of an enzymatic protein hydrolysate from the green microalga Chlorella vulgaris enhances the nutritional recovery of malnourished mice. 2166 89

Spontaneous motor activity and motor coordination were tested in adult female rats after treating with sodium fluoride at 20 or 40 mg/kg dose level daily for 60 days, using an activity chamber and a rota-rod apparatus, respectively. Total protein concentrations were determined in skeletal muscle, liver and serum of similarly treated animals. The activities of total cholinesterase and acetylcholinesterase were determined in blood and brain regions, respectively. Sodium fluoride treatment suppressed spontaneous motor activity. But no change was observed in the motor coordination of these animals. Tissue and serum protein concentrations were decreased. Cholinesterase activity was decreased in the blood and not in brain regions. A failure of sodium fluoride to impair motor coordination indicated that neuromuscular function required for a forced task was not deteriorated in these animals, although skeletal muscles were deprived of protein and blood cholinesterase activity was suppressed. A suppression of spontaneous motor activity suggests that fluoride has, by a central action, inhibited motivation of these animals to exhibit locomotor behavior. A cholinergic mechanism through a change in the activity of acetylcholinesterase may not account for this effect, since sodium fluoride treatment did not alter the activity this enzyme in brain regions. However, an involvement of monoamines may be proposed in view of previously reported finding that excessive fluoride intake has decreased the concentrations of 5-hydroxyindoleacetic acid and increased that of norepinephrine in rat brain.
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PMID:Effects of sodium fluoride on locomotor behavior and a few biochemical parameters in rats. 2178 93


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