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)

Omeprazole (CAS 73590-58-6), an H+, K+ ATPase inhibitor, is a potent suppressor of gastric acid secretion and a very active substance in the treatment of duodenal and gastric ulcers. The kinetic profile of omeprazole is well defined for healthy volunteers and for some high-risk population, but not so far for patients with liver disease. As the substance is mainly metabolized in the liver, changes in liver circulation and/or function might lead to changes in the pharmacokinetics of omeprazole. Aim of the study was to evaluate the kinetic profile in patients with liver disease and compare the results obtained in healthy volunteers, 16 subjects were included in the study: 8 patients with liver cirrhosis and 8 healthy volunteers. A single oral dose of omeprazole 20 mg was administered: plasma samples were collected for 24 h since omeprazole administration. The principal pharmacokinetic parameters were estimated for the two studied populations.
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PMID:Pharmacokinetics of omeprazole in cirrhotic patients. 185 16

Isolated human hepatocytes and separated neutrophils of 11 patients with alcoholic liver disease (ALD) were used to study some aspects of cellular calcium-related processes compared to nonalcoholic controls. 45Ca2+ efflux from the cells decreased in ALD and the calmodulin-inhibitor trifluoperazine did not influence it further. The intracellular free calcium concentration [( Ca2+]i) of nonstimulated hepatocytes and neutrophils proved to be higher in ALD with the Quin2/AM loading technique. However, the [Ca2+]i rise in hepatocytes and neutrophils, with stimulation by low density lipoprotein (LDL) and N-formyl-methionyl-leucyl phenylalanine (FMLP), respectively, was diminished in ALD compared to appropriate controls. The slower 45Ca2+ extrusion rate, higher basal [Ca2+]i levels, and the diminished [Ca2+]i elevation of activated hepatocytes and neutrophils, suggest disturbed calcium-related intracellular processes in ALD, in particular, impaired regulation of the plasma membrane Ca2(+)-ATPase.
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PMID:Disturbed intracellular calcium-related processes of hepatocytes and neutrophils in human alcoholic liver disease. 214 39

Mechanisms of alcoholic liver disease are still ill defined. We evaluated in two outbred lines of mice whether chronic ingestion of ethanol alters the lipid composition and/or enzyme activity of liver plasma membranes. Two mouse lines with different sensitivities towards the hypnotic effect of ethanol, designated long sleep and short sleep, were fed a liquid diet containing ethanol for 30 days. Ethanol intake reached 30 gm per kg per day in both lines, and serum ethanol levels were similar. In addition, hepatic triglyceride levels were similarly increased 2-fold with ethanol feeding. The following effects of ethanol treatment were observed in liver plasma membrane fractions: (i) Na+,K+-ATPase was significantly increased to 26% above control in long sleep only; (ii) alkaline phosphatase activity was 2-fold increased in both lines; (iii) 5'-nucleotidase, leucine aminopeptidase and Mg2+-ATPase activities remained unchanged in both lines; (iv) unesterified cholesterol and total phospholipid contents were unaltered in both lines, and (v) cholesteryl esters were increased in both lines, but to a greater extent in short sleep (1.5 vs. 4-fold). Thus, chronic ethanol ingestion induces specific alterations in liver plasma membrane structure and function, suggesting that adaptive responses to ethanol may be determined in part by inherited factors.
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PMID:Effect of chronic ethanol administration on enzyme and lipid properties of liver plasma membranes in long and short sleep mice. 299 Nov 3

There is increasing evidence for endogenous, circulating compounds that interact with the digitalis receptor of [Na,K]ATPase and with antidigoxin antisera. Circulating levels of these digitalis-like compounds increase in response to fluid or salt loading and appear to play a role in diseases characterized by fluid and salt retention, e.g. renal failure, liver disease, acromegaly, experimental and human hypertension, and preeclampsia. Because of assay nonspecificity, many diverse substances are being measured. Of the few compounds currently identified as having "digitalis-like" activity, none appears to be the natural ligand of the digitalis receptor and none appears linked with hypertension. Nevertheless, research still suggests that digitalis-like factors may have a central role in essential hypertension and related disorders.
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PMID:Endogenous digitalis-like natriuretic factors. 303 37

Six patients with varying degrees of renal insufficiency developed severe hyperkalemia following hepatic necrosis. The hyperkalemia was seen prior to or concomitant with marked elevations in hepatic enzymes. The basis of the liver disease appeared to involve congestive heart failure and/or hypotension. Necrotic liver cells released intracellular potassium into the blood of patients who were unable to handle the additional potassium load because of renal insufficiency and metabolic acidosis. Furthermore, a shift of potassium into the intracellular space is impaired in uremics by defective Na-K ATPase activity, possibly induced by uremic toxins. The 3 diabetic patients in our series may additionally have had aldosterone deficiency leading to impaired cellular potassium uptake.
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PMID:Hyperkalemia provoked by acute hepatic necrosis. 377 39

Common bile duct ligation (CBDL) in rats was used to induce liver disease and secondary kidney damage. The biochemical changes in the liver, kidney and plasma were studied at 3, 6, 10 and 21 days post CBDL. The observed alterations climaxed at the 6th day following ligation. Renal, activities of aldolase (ALD), lactic dehydrogenase (LDH), isocitric dehydrogenase (ICDH), sorbitol dehydrogenase (SDH), and alkaline phosphatase (ALP), were lowered in CBDL rats. Further, microsomal Na,K-ATPase and Mg-ATPase and mitochondrial oxidative-phosphorylation were inhibited. In the liver from CBDL rats the activities of aspartate aminotransferase (AST), Mg-ATPase and ALP were elevated, while SDH, ALD, malic dehydrogenase (MDH), LDH, malic enzyme (ME) and Na,K-ATPase were lowered. Plasma enzymes, AST, ALP, MDH, LDH, ALD, acid phosphatase (ACP) and ICDH and the metabolites bile acids, bilirubin, creatinine and urea were elevated. Addition of bile acids or bilirubin at concentrations comparable to those found in the plasma of CBDL rats, to the reaction mixture of the various enzymes strongly inhibited most, particularly mitochondrial oxidative phosphorylation. High concentrations of these substances in the blood may explain the development of renal failure during liver disease and its reversibility when liver function returns to normal.
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PMID:Biochemical changes in liver, kidney and blood associated with common bile duct ligation. 378 11

To elucidate possible causes of the hepatocyte swelling and necrosis found in alcoholic liver disease, the effects of ethanol and acetaldehyde on the activities of two hepatic plasma membrane ATPases--(Na+K+) ATPase and Mg2+ ATPase--were investigated. The activity of another plasma membrane-bound enzyme, 5' nucleotidase, was also determined to assess the specificity of these effects. Over concentrations ranging from 8 to 90 mM ethanol did not cause significant inhibition of any of the three enzymes. At 120 mM ethanol (Na+K+) ATPase activity was inhibited by 20% (P less than 0.01) and at higher concentrations there was progressive inhibition of all three enzymes that was non-competitive in type. Acetaldehyde produced non-competitive inhibition of (Na+K+) ATPase and Mg2+ ATPase at concentrations of 6 and 56 mM respectively and 5' nucleotidase activity was also inhibited at these concentrations. We conclude that ethanol and acetaldehyde inhibit (Na+K+) ATPase and Mg2+ ATPase activities as part of a generalised effect on the liver plasma membrane. Because the inhibitory concentrations of both substances are higher than are usually found in alcoholic subjects or in experimental animals after alcohol feeding, it seems unlikely that direct suppression of ATPase activity by ethanol or acetaldehyde is responsible for the morphological abnormalities of alcohol-induced liver disease. It could, however, be implicated in the development of hepatocellular necrosis in severe ethanol poisoning.
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PMID:Effects of ethanol and acetaldehyde on hepatic plasma membrane ATPases. 613 22

The heterogeneity of mitochrondrial autoantibodies in a variety of diseases states has been critically re-examined by a combination of immunofluorescence staining (IFL) and complement fixation tests (CFT). The different mitochondrial IFL patterns described by other workers were confirmed and extra criteria using new substrates are presented for their differential recognition. Biochemically defined mitochondrial subfractions were used in the CFT to confirm and extend the IFL classifications. The 'M1' cardiolipin antibodies of syphilis did not react with the ATPase fraction but the antigen was present in all membrane preparations and found to be chemically resistant. The major antibody specificity of the 'M3' pattern associated with drug-induced pseudolupus syndrome is a firmly bound, outer membrane component; and a second, minor reactivity is apparently to a mercurial-insensitive antigen present in the chloroform-released ATPase preparation. The 'M5' antibody pattern correlates with a digitonin-sensitive outer membrane component. Although it was not possible to differentiate within the group of liver diseases between the 'M2' antibodies of primary biliary cirrhosis and the previously described 'M4' antibodies of other chronic liver diseases, several antibody specificities were demonstrated. All sera from liver disease patients contain the antibody directed against a mercurial-sensitive protein found in the chloroform-released ATPase preparation, and, in addition, varying titres of antibodies against two or more mercurial-resistant membrane components, of which at least one is on the inner membrane and one on the outer membrane.
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PMID:Mitochondrial antibodies in chronic liver diseases and connective tissue disorders: further characterization of the autoantigens. 644 33

The pharmacology, pharmacokinetics, efficacy, safety, and dosage and administration of lansoprazole and omeprazole are reviewed. Lansoprazole and omeprazole are proton-pump inhibitors (PPIs). These agents bind covalently to hydrogen/potassium-exchanging adenosine triphosphatase in gastric parietal cells, rendering the molecule nonfunctional and inhibiting the secretion of gastric acid. The bioavailability of lansoprazole is 85%; that of omeprazole is 54%. Although lansoprazole and omeprazole have a plasma half-life of less than 2 hours, the duration of action is more than 24 hours. Clinical trials have shown lansoprazole and omeprazole to be effective in the treatment of duodenal ulcers, gastric ulcers, peptic ulcer disease involving Helicobacter pylori infection, recurrent ulcers, ulcers induced by nonsteroidal anti-inflammatory drugs, reflux esophagitis, Barrett esophagus, and Zollinger-Ellison syndrome. In many cases, these PPIs were more effective than histamine H2-receptor antagonists or worked when the latter failed. Lansoprazole and omeprazole have similar adverse-effect profiles and are well tolerated in both long- and short-term therapy. The dosage and duration of therapy vary with the condition being treated or the individual patient. Dosage adjustments should be considered only in the case of lansoprazole in patients with severe liver disease. Lansoprazole and omeprazole are highly specific in blocking a critical step in gastric acid production and have been found to be safe and effective in the treatment of many acid peptic disorders.
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PMID:Lansoprazole and omeprazole in the treatment of acid peptic disorders. 895 52

In the rapidly increasing elderly population, diarrhoea as a result of drug therapy is an important consideration. The elderly consume a disproportionately large number of drugs for multiple acute and chronic diseases. Drugs can compromise both immune and nonimmune responses. Aging decreases the quality and proportion of T cells which in turn reduces the production of secretory IgA, the primary immune response of the gut. Acid production in the stomach decreases with increasing age and this compromise its vital 'self-sterilising' function, thus increasing the risk of diarrhoea due to viral, bacterial and protozoal pathogens. Other nonimmune defence mechanisms include the motility of the small intestine and the host-protective commensal bacteria of the colon. Drug induced hypomotility may result in bacterial overgrowth, deconjugation of bile salts and diarrhoea. Less commonly, diarrhoea may occur due to hypermotility because of a cholinergic-like syndrome. In the colon the host-protective commensal bacteria provide a powerful defence against pathogens. Disruption of this commensal population by antibiotic therapy may result in Clostridium difficile supra-infection which causes diarrhoea through toxin production. This is especially important in the elderly patient on chemotherapy for malignancy and those with multiple diseases. The organism responds to vancomycin, metronidazole and bacitracin. Metronidazole is the suggested drug of choice, with vancomycin reserved for relapses. Drugs also cause diarrhoea by interfering with normal physiological processes. Drugs impair fluid absorption by activating adenylate cyclase within the small intestinal enterocyte which increases the level of cyclic AMP. This causes active secretion of Cl- and HCO3-, passive efflux of Na+, K+ and water and inhibition of Na+ and Cl- into the enterocyte. Examples of these drugs (secretagogues) are bisacodyl, misoprostol and chenodeoxycholic acid (used to dissolve cholesterol gallstones). Drugs may also affect a second mechanism that regulates water and electrolyte transport, the Na+, K+ exchange pump. The energy for this pump is provided by the ATPase mediated breakdown of ATP. ATPase may be inhibited by digoxin, auranofin, colchicine and olsalazine. A number of drugs cause osmotic diarrhoea including antacids containing magnesium trisilicate or hydroxide. Lactulose is being used increasingly in compensated liver disease to increase protein tolerance and prevent hepatic encephalopathy. Sorbitol, an osmotic laxative agent also used in some liquid pharmaceutical preparations, induces diarrhoea by virtue of its osmotic potential. Another mechanism by which drugs cause diarrhoea is by mucosal damage of the small and large bowel. In the small intestine mucosal damage causes diarrhoea and fat malabsorption, as may occur with neomycin and colchicine. In the colon, for example, gold salts and penicillamine cause colitis of varying severity. Though the causes of diarrhoea are diverse, a drug-associated aetiology should always be considered and actively sought and addressed to prevent the complications of dehydration, electrolyte imbalance and undernutrition.
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PMID:Mechanisms of drug-induced diarrhoea in the elderly. 978 28


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