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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that iodoarachidonates (IAs) prevent goiter production in rats. In the present studies we show that both IL-d and IL-w (IAs bearing the iodine atom at the positions 6 and 14, respectively), cause a significant involution of preformed goiter. This effect was evident when IAs were administered either orally or via i.p., although the first one required larger doses to obtain the same degree of inhibition. No changes were observed in serum protein, urea, cholesterol, cholinesterase, T3 or T4. In vitro studies with FRTL-5 cells showed that both IAs inhibit iodide and alpha-AIB uptake, as well as ATPase activity.
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PMID:Further studies on the antigoitrogenic action of iodoarachidonates. 128 29

Endogenous digitalis-like factor (EDLF), an inhibitor of membrane Na+/K(+)-ATPase, is discussed to be involved in the pathogenesis of cirrhogenic portal hypertension, ascites formation and development of functional hepatorenal failure. Therefore, we investigated the serum content of this mediator in patients with liver cirrhosis Child-Pugh stage A, B, and C (n = 27) by means of enzyme immunoassay with a specific digoxin antibody. Furthermore, a correlation analysis was performed in order to find out correlations between signs of cell injury, cholestasis, synthetic cell function, ascites formation, and hepatorenal failure. Our results demonstrate that EDLF is significantly elevated in Child C cirrhosis (0.61 +/- 0.15 ng/ml) in comparison to Child A cirrhosis (0.013 +/- 0.2 ng/ml) and is also higher than in Child B cirrhosis (0.23 +/- 0.25 ng/ml). In patients without ascites EDLF (0.056 +/- 0.19 ng/ml) differs significantly from that of patients with non-complicated ascites (0.156 +/- 0.176 ng/ml) and from that of patients with therapy refractory ascites (0.66 +/- 0.17 ng/ml) or hepatorenal failure (1.56 ng/ml). There are no correlations between EDLF and renal function. Significant correlations were demonstrated for cholestasis (serum bilirubin), synthesis function (serum protein, Quick's value, cholinesterase, fibrinogen, albumin), and the degree of portasystemic encephalopathy (number connection test). We conclude that EDLF may act as a mediator in the process of progressive portal hypertension and its complications due to cirrhosis. This process of progression is caused by the inhibition of Na+/K(+)-ATPase, vasoconstriction, and endothelin secretion.
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PMID:[Endogenous digitalis-like factor in liver cirrhosis and cholestasis]. 748 6

E3810 is a new H+,K(+)-ATPase inhibitor with a substituted benzimidazole, which is under clinical investigation for peptic ulcer treatment in Japan and the USA. Three separate studies were conducted to evaluate the safety and to establish the pharmacokinetic profile of E3810 after oral administration to healthy male subjects. E3810 was administered as: single oral doses (1, 3, 10, 20, 40 and 80 mg) in fasting conditions, a single oral dose (20 mg) after a meal and repeated oral doses (20 and 40 mg) once daily for 7 days. The concentrations of E3810 and its metabolites in plasma and urine were determined by HPLC methods with UV detection. E3810 was generally well tolerated by all subjects. In the single-dose study, Cmax and AUC increased with increasing doses in the dose range examined. The mean plasma half-life was about 1.0 hour and was dose-independent. The apparent oral clearance of E3810 ranged from 4.37 to 8.40 ml/min/kg. No significant deviation from linear pharmacokinetics was observed. Approximately, 30% of a dose was excreted into the urine as thioether carboxylic acid-E3810 and its glucuronide. The mean serum protein binding was 96.3%. No effect of food intake on the Cmax and AUC was observed while tmax after a meal was 1.7 hours longer than that in the fasting conditions. No appreciable change in drug pharmacokinetics was observed during repeated oral dosing of E3810.
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PMID:Pharmacokinetic properties of E3810, a new proton pump inhibitor, in healthy male volunteers. 782 Mar 29

Cataract is responsible for rendering several million people blind throughout the world and is also by far the most common cause of low visual acuity. Although cataract surgery is common, routine and effective, posterior capsule opacification (PCO) occurs in 30-50% of patients following modern cataract surgery. This condition arises from stimulated cell growth within the capsular bag after surgery. The resulting decline in visual acuity requires expensive laser treatment, and PCO therefore prevents modern cataract surgery from being carried out routinely in underdeveloped countries. The present study, using a human lens capsular bag culture system, has confirmed that cells from a wide age range of donors proliferate in the absence of added serum protein and explains why PCO is such a common problem even in aged patients. This study also provides one possible solution for PCO by using polymethylmethacrylate (PMMA) implanted intraocular lenses as a drug delivery system. PMMA lenses coated with thapsigargin, a hydrophobic inhibitor of endoplasmic reticulum (ER) (Ca2+)-ATPase, greatly reduced cell growth in the capsular bag at relatively low coating concentrations (200 nM) but, more significantly, induced total cell death of the residual anterior epithelial cells at higher concentrations (>2 microM).
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PMID:Thapsigargin-coated intraocular lenses inhibit human lens cell growth. 928 18

Swiss albino rats were treated in groups with CCl4, and flyash to induce cellular toxicity in the lungs and trachea. Animal groups received treatment of Koflet (K) with CCl4 (7 days) and with flyash (30 days); their general health and biochemical parameters were studied and used as an indication of cellular injuries. A significant loss was observed in body weight and food consumption in animals given only CCl4 or flyash, while simultaneous treatment with K resulted in a non significant alteration from normal control groups. Enzyme (alkaline phosphatase, Ca2+ -Mg2+ -ATPase, glutamic-oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT)) activities were estimated in tissue homogenate preparation of lung, trachea and serum, which showed no significant change except for GPT activity as compared to control animals which received CCl4 or flyash with K. Similarly lung, trachea and serum contents of carbohydrate, protein, sialic acid, serum protein, serum cholesterol were estimated and it was found that alteration caused by CCl4, or flyash becomes almost non-significant compared to that of the control after the treatment of K, except for carbohydrate and serum cholesterol values. The animal group which was only treated with K did not show any significant alteration in their biochemical markers or injuries, except for cholesterol.
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PMID:In vivo protective role of Koflet (an ayurvedic preparation) against cellular toxicity caused by CCl4 and flyash. 940 99

Gastric proton pump inhibitors (PPIs) are substituted benzimidazole prodrugs that require an acid-induced activation. Its rate depends on the reactivity of the molecule relative to the environmental pH and determines the drug's tissue selectivity. Factors affecting the exposure of moderately acidic tissues to the activated PPI are the area under the serum concentration-time curve (AUC), serum protein binding, the partition coefficient logP and the serum elimination half-life relative to the chemical activation half-life at a critical tissue pH of about 5. These parameters have therefore been determined in a comparative fashion in the present study. The data shows that pantoprazole is less likely to undergo unwanted activation at moderately acidic targets as opposed to the parietal cell, compared to omeprazole. Actually, although 40 mg pantoprazole (steady state) gave a slightly higher serum AUC of the total parent compound than 40 mg omeprazole (10.5 vs. 7.1 micromol x h x l[-1]), a higher serum protein binding of pantoprazole versus omeprazole (98 vs. 96%) reversed the AUC values for the free drug in favor of a lower value for pantoprazole (0.19 vs. 0.28 micromol x h x l[-1]). It is the free parent compound that equilibrates across cell membranes to be activated in acidic tissue compartments. At pH 5.1, the activation half-life of pantoprazole was 4.7 versus 1.4 h for omeprazole, the latter being in the order of the common serum elimination half-life determined in an intraindividual comparison (1.24 vs. 1.25 h). Thus, pantoprazole is eliminated faster from blood than it is activated at a pH of about 5, while omeprazole is as quickly activated at this pH as it is eliminated from blood. Biological in vitro experiments confirmed that pantoprazole displays a lower liability to interfere with unwanted biological targets. This has been demonstrated in vitro for inhibition of both renal Na+/K+-ATPase, lysosomal acidification and the production of reactive oxygen species by neutrophils.
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PMID:Differences in pH-dependent activation rates of substituted benzimidazoles and biological in vitro correlates. 949 64

The effect of two new chelating agents-Tiron (4,5-dihydroxy-1,3-benzene disulphonic acid disodium salt) and succinic acid--on the mobilization of beryllium was studied. Animals were exposed to beryllium nitrate (1 mg kg(-1) i.p.) daily for 21 days. Administration of beryllium nitrate showed a marked decrease in haemoglobin percentage, blood sugar, serum alkaline phosphatase and serum protein and a significant increase in the activity of transaminases. Tissue protein and glycogen contents and the activity of alkaline phosphatase, adenosine triphosphatase and succinic dehydrogenase showed significantly decreased values, but beryllium nitrate provoked a considerable increase in the activity of acid phosphatase and glucose-6-phosphatase in the vital and reproductive organs. Significant improvement in the haematological and biochemical parameters was observed with Tiron but no therapeutic effect was seen with succinic acid. Atomic absorption spectrophotometry (AAS) also showed a decreased level of beryllium concentration in the liver and kidney after Tiron therapy.
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PMID:Influence of chelating agents on the toxicity and distribution of beryllium in rats. 980 33

Human serum albumin (HSA) is a cystine-rich serum protein taken up by many cells through receptor-mediated and fluid-phase endocytosis. We hypothesized that HSA may play a role in modulating cellular antioxidant redox signaling. Lung epithelial cells (A549), fibroblasts (HFL1), and blood lymphocytes had increased glutathione (GSH) levels after 8 h incubation with HSA. Similar GSH increases were observed with either plasma-derived or recombinant HSA. Serum depleted of HSA had no effect on cellular GSH. The GSH increase was also observed in normal murine lungs upon in vivo airway instillation of HSA. GSH enhancement was not related to the redox state of the free cysteine residue (Cys-34) on HSA, however, reduction of disulfide bonds in HSA inhibited the increase in cellular GSH. In addition, the albumin-mediated increase in GSH was inhibited by the vacuolar (H(+))-ATPase inhibitors, bafilomycin A(1) and concanamycin, as well as by the membrane pH-disrupting ionophore monensin, but not by 20 mM NH(4)Cl. The degree to which albumin increased GSH levels was sufficient to protect cells against H(2)O(2)-mediated cytotoxicity and to decrease TNF-alpha-mediated NF-kappaB activation. We conclude that albumin specifically modulates cellular GSH levels, an effect sufficient to protect cells against oxidant injury and regulate NF-kappaB activation.
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PMID:Albumin-mediated regulation of cellular glutathione and nuclear factor kappa B activation. 1102 74

The efficacy of Tiron (4,5-dihydroxybenzene 1,3-disulfonic acid disodium salt) was examined in the treatment of beryllium-induced maternal and developmental toxicity in rats. Single administration of beryllium nitrate at a dose of 50 mg/kg (i.m.) on day 13 of gestation caused reductions in fetal and placental weights, the number of implantation sites and number of corpora lutea, as well as causing post-implantation loss, stunted growth, increase in the number of resorptions, and also a disturbed sex ratio. Maternal toxicity was demonstrated by reduction in body weight gain. Administration of beryllium also showed significant alteration in the hematological and biochemical indices of the mother as well as the fetus. Marked decreases were recorded in hemoglobin percentage, blood sugar levels, serum protein contents and serum alkaline phosphatase activity. By contrast, significant elevation was found in the activity of transaminases (aspartate aminotransferase and alanine aminotransferase). Tissue protein contents, glycogen contents, activities of alkaline phosphatase, adenosine triphosphatase and succinic dehydrogenase of kidney, lungs and uterus, and maternal and fetal liver all showed significantly decreased values after beryllium exposure, and remarkable elevation was observed in acid phosphatase, glucose-6-phosphatase and hepatic lipid peroxidation. These parameters were restored considerably with administration of 471 mg/kg i.m. Tiron from days 14 to 18 of gestation. Atomic absorption spectrophotometry also revealed a high concentration of beryllium in different organs of pregnant rats. Interestingly, a small amount of metal ion was also detected in the fetus and reduced accumulation of beryllium was noticed after Tiron treatment.
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PMID:Protective effect of Tiron (4,5-dihydroxybenzene-1,3-disulfonic acid disodium salt) against beryllium-induced maternal and fetal toxicity in rats. 1218 11

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


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