Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sensitive, specific, and simple method for determining serum or urine arylesterase (EC 3.1.1.2) is described. The enzyme acts on phenyl acetate to release phenol, which produces a stable indophenol dye with 4-aminoantipyrine and potassium ferricyanide. Arylesterase, a thiol enzyme, is reactivated by 2-mercaptoethanol and by cysteine, but not by reduced glutathione. Calcium is indispensable to stabilize and to activate (Km = 0.85 mmol/L) the enzyme; complete protection is achieved at CaCl2 20 mmol/L. Magnesium acts as a weak (Ki = 116 mmol/L), lanthanum as a potent (Ki = 5 mumol/L) competitive inhibitor. The activity is measured in diluted sera at phenyl acetate 4.0 mmol/L (Km = 1.12 mmol/L), pH 7.8 and 25 degrees C. The normal range extends from 53 to 186 kU/L, and four isoenzymes are present in sera from healthy adults. Arylesterase decreases in hepatic disorders, especially in cirrhosis and carcinoma of the liver, with reduction of the penultimate fraction in polyacryalmide gel electrophoresis.
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PMID:Arylesterase in serum: elaboration and clinical application of a fixed-incubation method. 47 20

Magnesium deficiency can occur in congestive heart failure, after diuresis with furoxemide, ethacrynic acid and mercurials, and with digitalis intoxication, diabetic acidosis, acute and chronic alcoholism, delerium tremens, cirrhosis, malabsorption syndromes, protracted postoperative cases, open heart surgery, the diuretic phase of acute tubular necrosis, and with hypoparathyroidism, primary aldosteronism, juxta-glomerular hyperplasia and pancreatitis. Two cases of serious ventricular arrhythmias associated with magnesium depletion are described. Clinical manifestations are vague but center around neurologic symptoms such as weakness, tremors, stupor, coma, nausea, vomiting and anorexia. Serious cardiac arrhythmias also occur with magnesium depletion. Magnesium appears to be very useful in hypomagnesemic or digitalis-toxic tachyarrhythmias. Magnesium may also be valuable in normomagnesemic tachyarrhythmias. Ten to fifteen milliliters of a 20 percent magnesium sulfate solution, given intravenously over 1 minute, followed by a slow 4 to 6 hour infusion of 500 ml of 2 per cent magnesium sulfate in 5 per cent dextrose in water is recommended. Recurrence of arrhythmias is common and a second infusion of magnesium sulfate may be necessary. Hypermagnesemia occurs frequently in renal insufficiency, and magnesium therapy may then be contraindicated. Serum levels above 5.5 meq/liter should be avoided. Loss of deep tendon reflexes and a decrease in respiratory rate can be used as guides to magnesium therapy. A plea is made for frequent analysis of serum magnesium so that more knowledge can be gained regarding this important biologic element in cardiovascular disorders.
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PMID:Magnesium deficiency and cardiac disorders. 80 29

The in vivo formation of the sulfate ester of glycolithocholate is a critical step in the elimination of this hepatotoxic bile salt. Rhesus monkeys fed chenodeoxycholate or ursodeoxycholate, the precursors of lithocholate, develop frank cirrhosis in association with accumulation of nonsulfated glycolithocholate in bile. An enzyme catalyzing the formation of glycolithocholate-3-sulfate has been isolated from hepatic cytosol of adult female rhesus monkeys and has been purified 146-fold. When reduced it appears as a 30 kD band on an SDS-polyacrylamide gradient gel. It has a pH optimum of 7.0 and is stimulated by low concentrations of Mg2+ (up to 2 mM), but does not have an absolute requirement for this metal ion. The kinetics of this enzyme have been investigated to ascertain whether its reaction mechanism can account for the poor in vivo rate of glycolithocholate sulfation. Inhibitor studies with an oxidized metabolite of lithocholate, 3-keto-5 beta-cholanoate, showed that the latter is a competitive inhibitor of glycolithocholate and is noncompetitive with the active form of sulfate, 3'phosphoadenosine-5'-phosphosulfate. The monophosphonucleotide 3'-AMP is a competitive inhibitor of 3'phosphoadenosine-5'-phosphosulfate, and is noncompetitive with glycolithocholate. These observations are consistent with a sequentially ordered Bi Bi reaction mechanism in which the bile salt is the first substrate to bind to the enzyme. Such a reaction mechanism for bile salt:3'phosphoadenosine-5'-phosphosulfate:sulfotransferase would be, therefore, the first time in which the sulfate acceptor (the bile salt) is the initial substrate to bind to a sulfotransferase. These studies have shown that although rhesus monkeys have a liver enzyme capable of forming the sulfate ester of glycolithocholate, its reaction mechanism and the potent inhibition caused by simple metabolites, such as 3-keto-5 beta-cholanoate, may serve to under-express the activity of the enzyme in vivo.
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PMID:Evidence for an ordered reaction mechanism for bile salt: 3'phosphoadenosine-5'-phosphosulfate: sulfotransferase from rhesus monkey liver that catalyzes the sulfation of the hepatotoxin glycolithocholate. 347 Apr 20

In 4 patients with nonalcoholic liver cirrhosis, the incomplete form of distal renal tubular acidosis was demonstrated by the CaCl2 load test. Mg replenishment corrected the acidification defect.
Magnesium 1986
PMID:Magnesium-responsive incomplete distal renal tubular acidosis in patients with liver cirrhosis. 395 96

Low serum, cerebrospinal fluid, erythrocyte, muscle and bone Mg concentrations have been found in liver cirrhosis, indicating a Mg deficiency. Decreased intake, fat malabsorption, renal tubular acidosis and increased serum levels of aldosterone, growth hormone and glucagon could be the causative factors.
Magnesium 1985
PMID:Magnesium and liver cirrhosis: a hypothesis. 403 1

Renal excretion, skeletal muscle content and plasma concentration of electrolytes were studied in 108 patients on long-term diuretic therapy for congestive heart failure and/or arterial hypertension. As reference populations served a group of 16 healthy volunteers and a group of 22 patients with liver cirrhosis, but not on diuretic therapy. Diuretic therapy was found to deprive the patients of their ability to conserve potassium and magnesium when there was a simultaneous cellular depletion of these ions. Magnesium excretion was found to be correlated to the skeletal muscle magnesium content. An inverted Na/K ratio in urine and a low magnesium excretion were fair indicators of cellular magnesium depletion.
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PMID:Renal excretion of electrolytes in patients on long-term diuretic therapy for arterial hypertension and/or congestive heart failure. 409 Oct 44

Energy-rich phosphagens, water, and electrolytes were determined in skeletal muscle biopsy specimens from five elderly women and five elderly men with moderate liver cirrhosis. At the time of the study the patients were in their usual condition without evidence of deterioration of the disease. When compared with findings in apparently healthy subjects of similar age, the distribution and level of electrolytes and water were within normal limits in the female patients. The male patients showed increased contents of muscle water, and Mg2+ was reduced. The values calculated for the intracellular concentration of K+ and Mg2+ were also below normal. The pattern and levels of energy-rich phosphagens were abnormal in all but one female patient. As a general finding, ATP and the total level of adenine nucleotides were markedly reduced, as were phosphocreatine, the ATP/ADP ratio, and the energy charge potential.
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PMID:Muscle biopsy studies in patients with moderate liver cirrhosis with special reference to energy-rich phosphagens and electrolytes. 671 37

Concentrations of apoprotein A in whole serum, and cholesterol and phospholipids concentrations in the high-density lipoprotein fraction of serum were measured after the precipitation of low-density and very-low-density lipoproteins with sodium phosphotungstate-Mg2+ in 23 patients with liver cirrhosis, 19 patients with extrahepatic biliary obstruction, and 20 healthy control subjects. Patients with cirrhosis and cholestasis showed approximately one-half as much cholesterol and apoprotein A in the nonprecipitable high-density lipoprotein fraction as normal subjects did. High-density lipoprotein phospholipids concentrations in those patients were normal or slightly increased, however, which is about double what one would expect from the apoprotein A and cholesterol content.
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PMID:High-density lipoprotein cholesterol and phospholipids, and apoprotein A in serum of patients with liver disease. 706 98

Magnesium status of Indian patients with cirrhosis of liver (alcoholic and non alcoholic) and the role of low magnesium in neuromuscular and neuropsychiatric manifestations of chronic liver disease were evaluated in 76 male cirrhotics (alcoholic 37, aged 48 +/- 11 yr, non alcoholic 39, aged 47 +/- 12 yr) and 37 male controls (aged 49 +/- 11 yr). Serum magnesium levels were similar in the 3 groups studied. Muscle magnesium in both groups of cirrhotics were significantly lower than in controls (alcoholic cirrhosis 33.77 +/- 16.85; non alcoholic cirrhosis 37.93 +/- 18.86 and controls 70.52 +/- 6.49 mEq/kg fat free dry mass; P < 0.001). Multiple regression analysis comparing muscle magnesium with clinical and biochemical parameters in cirrhosis showed that hepatic encephalopathy was associated significantly and independently with low muscle magnesium (Beta = -0.313; P = 0.01). These results indicate that patients with cirrhosis have significantly lower muscle magnesium than controls and suggests that low muscle magnesium may be a factor associated with or precipitating hepatic encephalopathy.
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PMID:Serum & muscle magnesium in Indians with cirrhosis of liver. 941 43

Xipamide (CAS 14293-44-8) shows structural features comparable with the thiazide- as well as the class of loop diuretics. According to earlier findings this diuretic, in contrast to the thiazides, should not decrease the glomerular filtration rate (GFR) and be effective even in patients with advanced renal failure. Therefore recently the question, which class of diuretics xipamide should be related to, has been increasingly discussed. In order to solve this issue, the diuretic effect of xipamide was assessed in healthy volunteers once without and once under strict water and salt restriction. Additionally, changes in GFR were monitored by means of measurement of the creatinine clearance. Kinetic parameters were determined in plasma and urine; further, in patients with liver cirrhosis, renal elimination kinetics of the diuretic were correlated with the concentration of direct plasma bilirubin, as a marker of cholestasis, at the beginning of a treatment with xipamide, 40 mg qd. The investigations proved that xipamide, like a typical thiazide diuretic, gives rise to a temporary decrease in GFR of about 30 %, provided the renin-angiotensin-aldosterone system of the volunteer is activated by previous salt and water restriction. Xipamide leads to an increase of K+ and Mg2+ excretion, but to a decrease of Ca2+ excretion in urine, a charactaristical feature of the thiazide-like diuretics. The correlation between Na+ excretion and drug excreted in urine over time showed a functional graph that is characteristic for a "low ceiling" thiazide diuretic. In patients with renal failure FE(Na) was increased when related to the GFR-adjusted drug excretion rate, whereas it was diminished in conditions with decreased effective circulating volume like in liver cirrhosis with ascites. It could be shown that the elimination kinetics of xipamide are determined by renal drug clearance, which proportionally decreases with GFR. In patients with liver failure, a decrease of non-renal drug clearance went along with an increase in urinary drug excretion. The amount of drug excreted in urine (Ae) proportionally increased with the concentration of the patients' direct plasma bilirubin. Thus, from a pharmacological as well as clinical point of view xipamide acts like a thiazide diuretic. As could be shown for other thiazides some time ago, xipamide is effective not only in patients with cardiovascular diseases, but also in those with advanced renal failure.
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PMID:[Mechanism of action of xipamide and its classification as a "low ceiling diuretic". Pharmacodynamic-pharmacokinetic studies in healthy volunteers and in kidney and liver patients]. 1572 59


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