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)

This paper reviews the principal effects of phenobarbital on biliary function. Phenobarbital administration is followed by an increase in bile flow. This is mainly due to an increase in the bile salt-independent fraction of canalicular bile flow possibly through an increase in canilicular Na+-K+ ATPase activity. In addition, bile salt excretion may be increased. This effect of barbiturates on choleresis appears to be independent of microsomal enzyme induction. Barbiturates increase the uptake, storage and excretion of various dyes, for example sulfobromophthalein. Phenobarbital increases bilirubin clearance by the liver; it enhances bilirubin-UDP-glucuronyl transferase activity; whether the influence on bilirubin clearance is related to the effect on the enzyme is unknown. The influence of phenobarbital on biliary lipids is markedly different from one species to the other. In the rhesus monkey and in the rat, the relative concentration of cholesterol is decreased; in the hamster it is increased, and in man it appears largely unaffected. These effects of phenobarbital have been utilized in the treatment of chronic unconjugated hyperbilirubinemia and of certain cholestatic syndromes. Phenobarbital alone has been useful, so far, in the treatment of cholesterol gallstones.
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PMID:Barbituates and biliary function. 12 85

Eighteen dogs were studied for 54 days. Rectal mucosal electrical potential difference (PD), gallbladder bile acids, cholesterol, and phospholipids were measured. It was shown that feeding chenodeoxycholic acid (CDCA) for 24 days in dosages of 15, 30, and 60 mg/kg of body weight, all depressed PD equally but significantly (P less than 0.05) in three groups of dogs compared with a control group. This depression was reversible 24 days after CDCA ingestion ceased in the two highest dosages. The low dose group was sacrificed after 24 days of CDCA feeding and the gallbladder bile was analyzed. CDCA and cholesterol were each significantly (P less than 0.05) elevated over control values in the gallbladder bile of these dogs. Phospholipids were not significantly changed. The PD, a reflection of Na+ -K+ ATPase activity, may be a useful indicator in maximizing dosages of CDCA in gallstone dissolution studies.
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PMID:Changes in electrical potential difference of rectal mucosa and of gallbladder bile constituents of dogs fed chenodeoxycholic acid. 379 Oct 47

It has been found in this laboratory that proglumide (PGM) can increase hepatic bile flow in humans and in several species of animals, and lower gallstone formation in experimental animals. In order to further investigate the mechanisms of this choleretic effect of PGM, studies with isolated rat liver cells and plasma membranes were performed. The results indicated that PGM could increase the activity of membrane Na+, K(+)-ATPase significantly. On the other hand, PGM decreased the net uptake of 14C-glycocholic acid by rat liver cells. These data suggest that the choleretic effect of PGM is likely to be mediated through the enhancement of membrane Na+, K(+)-ATPase activity (which would in turn increase water and electrolyte output), rather than by affecting bile acid uptake by liver cells. It was also observed that PGM could reverse the inhibitory effect of somatostatin on the activity of membrane Na+, K(+)-ATPase. These results provide some clues for the elucidation of the mechanisms of the inhibitory effect of PGM on gallstone formation in experimental animals.
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PMID:[A study on the mechanism of the choleretic effect of proglumide]. 791 71

The protective effect of alcohol against cholesterol cholelithiasis has been established in several epidemiologic studies. An impairment of gallbladder motility in gallstone disease has been demonstrated in animals and in man. At a daily dose of 39 g, alcohol reduces the lithogenic index of bile, but its effect on gallbladder motility is still debated. To test this potential mechanism, the effect of 20 g of alcohol on gallbladder motility was studied, using an ultrasonographic ellipsoid method in 16 healthy male subjects. The stimulus for gallbladder contraction was a Lundh test meal. Using a cross over method, this meal was ingested by each subject once with water and once with alcohol. A third set of measurements was taken in each subject after ingestion of a Lundh meal and water to test the reproducibility of the sonographic method. The gallbladder kinetics were studied for 90 minutes following ingestion of the test meal and beverage. Alcohol stimulated rapid post prandial gallbladder emptying, and accelerated gallbladder filling. This second action could result from sphincter of Oddi pressure enhancement and, perhaps, decrease of gallbladder absorption by Na+ K+ ATPase inhibition. The reproducibility of the method was good. With a decrease of lithogenic bile index, the protective effect of alcohol against biliary cholesterol cholelithiasis could be due either to stimulation of gallbladder emptying and/or acceleration of gallbladder filling.
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PMID:[Ultrasound study of gallbladder motility in healthy subjects. Reproducibility of the method and effect of alcohol]. 814 51

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

Intracellular Ca(2+)-changes not only participate in important signaling pathways but have also been implicated in a number of disease states including acute pancreatitis. To investigate the underlying mechanisms in an experimental model mimicking human gallstone-induced pancreatitis, we ligated the pancreatic duct of Sprague-Dawley rats and NMRI mice for up to 6 h and studied intrapancreatic changes including the dynamics of [Ca(2+)](i) in isolated acini. In contrast to bile duct ligation, pancreatic duct obstruction induced intra-pancreatic trypsinogen activation, leukocytosis, hyperamylasemia, and pancreatic edema and increased lung myeloperoxidase activity. Although resting [Ca(2+)](i) in isolated acini rose by 45% to 205 +/- 7 nmol, the acetylcholine- and cholecystokinin (CCK)-stimulated calcium peaks as well as the amylase secretion declined, but neither the [Ca(2+)](i)-signaling pattern nor the amylase output in response to the Ca(2+)-ATPase inhibitor thapsigargin nor the secretin-stimulated amylase release were impaired by pancreatic duct ligation. On the single cell level pancreatic duct ligation reduced the percentage of cells in which submaximal secretagogue stimulation was followed by a physiological response (i.e. Ca(2+) oscillations) and increased the percentage of cells with a pathological response (i.e. peak plateau or absent Ca(2+) signal). Moreover, it reduced the frequency and amplitude of Ca(2+) oscillation as well as the capacitative Ca(2+) influx in response to secretagogue stimulation. Serum pancreatic enzyme elevation as well as trypsinogen activation was significantly reduced by pretreatment of animals with the calcium chelator BAPTA-AM. These experiments suggest that pancreatic duct obstruction rapidly changes the physiological response of the exocrine pancreas to a Ca(2+)-signaling pattern that has been associated with premature digestive enzyme activation and the onset of pancreatitis, both of which can be prevented by administration of an intracellular calcium chelator.
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PMID:Early changes in pancreatic acinar cell calcium signaling after pancreatic duct obstruction. 1252 41

The role of the isoprenoid pathway in gastrointestinal and hepatic diseases, and its relation to hemispheric dominance, was assessed in this study. The following parameters were measured in patients with (i) acid peptic disease, (ii) ulcerative colitis, (iii) gallstones, (iv) cryptogenic cirrhosis liver, (v) Reye's syndrome, (vi) mesenteric artery occlusion, (vii) irritable bowel syndrome, and (viii) in individuals with right hemispheric, left hemispheric, and bihemispheric dominance: 1. plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; 2. tryptophan/tyrosine catabolic patterns; 3. free radical metabolism; 4. glycoconjugate metabolism; and 5. membrane composition. In patients with gastrointestinal and hepatic disease there were elevated digoxin synthesis, increased dolichol, and glycoconjugate levels, and low ubiquinone and elevated free radical levels. The RBC membrane Na(+)-K+ ATPase activity and serum magnesium were decreased. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites in the serum. There was an increase in cholesterol: phospholipid ratio and a reduction in the glycoconjugate level of RBC membrane in these groups of patients. The same biochemical patterns were obtained in individuals with right hemispheric dominance. An upregulated isoprenoid pathway and hyperdigoxinemia is characteristic of gastrointestinal and hepatic disease and in right hemispheric chemical dominance. Right hemispheric chemical dominance is important in deciding the predisposition to gastrointestinal and hepatic disease.
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PMID:Hypothalamic digoxin, cerebral chemical dominance, and regulation of gastrointestinal/hepatic function. 1269 Oct 2

This article is based on the experience of 320 patients with Wilson's disease who were seen between the years 1954 and 2000. These patients were seen at The Boston City Hospital, 1954 thru 1955, University College Hospital, London,1955 thru 1957; Addenbrooke's Hospital, Cambridge, 1967 thru 1987, and The Middlesex Hospital London, 1988 thru 2000. Wilson's disease is not strictly a gastroenterologic disease but a genetically determined metabolic disease that is mediated by a failure of copper excretion through the bile. The mutation carried on chromosome 13q14.3: it involves a copper-carrying ATPase (ATPase 7B); more than 250 mutations are now known. The first organ to be affected is the liver, then many other tissues, principally the brain but also the eyes, the kidneys, the bone marrow, and the osteoskeletal system. It is with the hepatic form of the disease that this article is concerned. The hepatic illness may be acute, subacute or chronic; it may be progressive or, apparently, self-limiting. In 10% of patients hemolysis may also be found which can later lead to the formation of pigment gallstones. The management of liver disease is not considered in this article, which is strictly confined to the therapeutic options available for the elimination of copper and the long-term welfare of the patient. It must be remembered that all close relatives of the patient must be screened for the presymptomatic stage of the disease so, if they are found to be homozygous carriers for the mutation, they can be started on preventive treatment.
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PMID:Hepatic Wilson's disease: initial treatment and long-term management. 1631 64

Cholangiocarcinoma is a highly malignant form of gastrointestinal cancer with an unfavorable prognosis. The novel oncogene chromodomain helicase/ATPase DNA binding protein 1-like (CHD1L) has been confirmed to serve a vital role in numerous types of cancer, including liver cancer. Mismatch repair (MMR) is a common DNA repair process that contributes to the preservation of the integrity and stability of genetic substances. Human mutL homolog 1 gene (hMLH1) is an important MMR protein family member. The present study aimed to evaluate the pathological and clinical features of cholangiocarcinoma, and to investigate the clinical significance of CHD1L and hMLH1 expression in cholangiocarcinoma. A total of 108 samples from cholangiocarcinoma tumor tissues and 60 samples from normal bile duct tissue were obtained from patients admitted to The Second Affiliated Hospital of Nanchang University between May 2005 and May 2014. All cholangiocarcinoma cases were pathologically confirmed. The expression of CHD1L and hMLH1 was examined by immunohistochemistry analysis. The expression of CHD1L in cholangiocarcinoma (94.44%) was significantly higher than in normal bile duct tissues (40.00%). CHD1L expression was associated with gallstone history, serum carbohydrate antigen 19-9 (CA19-9) level and Tumor-Node-Metastasis (TNM) stage (P<0.05). hMLH1 expression in cholangiocarcinoma (77.78%) was significantly lower than in normal bile duct tissues (96.67%), and was associated with gender, age, serum CA19-9 level, the presence of hepatitis B virus surface antigen, TNM stage and tumor diameter (P<0.05). Kaplan-Meier survival curve analysis indicated that the 3-year accumulative survival rates for CHD1L-positive and -negative patients differed significantly (P<0.05; 17.90 and 83.33%, respectively). There was no statistically significant difference (P>0.05) between the 3-year accumulate survival rates for hMLH1-positive and -negative patients (38.90 and 33.30%, respectively). High CHD1L expression and low hMLH1 expression levels were observed in patients with cholangiocarcinoma, and their abnormal expression patterns were associated with the progression of malignancy and an unfavorable disease prognosis. Therefore, CHD1L and hMLH1 may be potential prognostic biomarkers for cholangiocarcinoma.
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PMID:Clinical significance of chromodomain helicase/ATPase DNA binding protein 1-like and human mutL homolog 1 gene expression in cholangiocarcinoma. 3012 88