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)

The major biological functions of S-adenosyl-L-methionine (SAMe) include methylation of various molecules (transmethylation) and synthesis of cysteine (trans-sulphuration). A stable double salt of SAMe has been found to be effective in intrahepatic cholestasis. The mechanism of its therapeutic effect is not fully understood but presumably involves methylation of phospholipids. Methylation of plasma membrane lipids may affect membrane fluidity and viscosity, which modulate the activities of a number of membrane-associated enzymes, for example, the activity of enzymes involved in Na+/Ca++ exchange (e.g. sarcolemmal vesicles), Na+/K+ adenosine triphosphatase (ATPase) [e.g. hepatocyte plasma membranes], and Na+/H+ exchange (e.g. plasma membranes of colonic cells). Recently, patients with cirrhosis were shown to have an acquired metabolic block in the hepatic conversion of methionine to SAMe. These patients, when administered conventional elemental diets, develop abnormally low plasma concentrations of cysteine and choline, 2 nonessential nutrients present in low concentrations in most elemental diets. These low concentrations probably reflect systemic deficiencies attributable to reduced endogenous syntheses of cysteine and choline caused by limited availability of hepatic SAMe. Such cirrhotic patients are often in negative nitrogen balance and have abnormal hepatic functions, which are corrected by cysteine and choline supplements. Noncirrhotic patients on parenteral elemental diets also become deficient in cysteine and choline. Consequently, these patients may require SAMe as an essential nutrient to normalise their overall hepatic transmethylation and trans-sulphuration activities.
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PMID:Biochemistry and pharmacology of S-adenosyl-L-methionine and rationale for its use in liver disease. 208 85

It has been suggested that sodium renal excretion is regulated, at least partially, by a factor with natriuretic properties called digoxin-like factor (DLF). As this substance crossreacts with digoxin antibodies, it was measured with a radioimmunoassay used to determine exogenous digoxin. Methodological conditions and quality control to determine DLF in plasma and urine have been established. Good correlation coefficients in specificity as well as dilution studies were obtained. Within--and between--assay coefficients of variations indicate good reproducibility. Moreover, changes in plasma DLF levels were detected in patients with cirrhosis or with renal failure, diseases which thrive on alterations in salt and water metabolism. In conclusion, this radioimmunoassay method for measuring DLF may be useful to investigate the role of this factor in several physiological and pathological conditions.
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PMID:[Developement and quality control of a radioimmunoassay for measurement of endogenous digoxin]. 209 36

Nutritional support in patients with advanced cirrhosis is difficult due to protein, fluid and salt restrictions. Successful liver transplantation should improve nutrient tolerance. We randomly assigned 28 hypoalbuminemic cirrhotic patients to receive, immediately after liver transplantation, one of three regimens: group 1, no nutritional support (n = 10); group 2, total parenteral nutrition (TPN) (35 kcal/kg/day) with standard amino acids (1.5 g/kg/day) (n = 8); or group 3, isocaloric isonitrogenous TPN with added branched-chain amino acids (n = 10). Therapy was continued for 7 days posttransplant. Jaundice resolution was unaffected by nutritional support. Nitrogen balance favored both TPN groups. Branched-chain amino acid (BCAA) aromatic amino acid ratios were highest in group 3. Coma scores and serum ammonia levels were similar in all groups. Both TPN groups achieved respirator independence earlier; this difference was not statistically significant. Group 1 patients stayed longest in ICU; the difference was statistically significant. TPN with either standard or BCAA- enriched amino acids is tolerated well immediately after successful liver transplant. Positive nitrogen balance is achieved; large protein loads do not worsen encephalopathy. Nutritional support may improve respiratory muscle function, allowing earlier weaning from ventilatory support. A shortened length of ICU stay justifies the expense of TPN.
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PMID:Nutritional support after liver transplantation: a randomized prospective study. 179 69

The heart atrium, as well as under certain pathophysiological conditions the ventricle, synthesize and release ANP. Exerting natriuretic, diuretic and vasorelaxant effects, this peptide plays an important role in the body's blood volume and blood pressure homeostasis. Whereas the pharmacological actions of ANP have been quite convincingly demonstrated, its physiological and pathophysiological role is less well defined. ANP plasma levels tend to be increased in diseases with salt and water retention, such as essential hypertension, congestive heart failure, renal failure or liver cirrhosis. With regard to its hemodynamic effects, ANP seems to be beneficial in patients with hypertension. ANP appears to have little therapeutic potential as a diuretic in patients with congestive heart failure and liver cirrhosis, possibly due to the decreased renal responsiveness to ANP in these diseases. However, ANP might to be a valuable therapeutic agent in acute renal failure.
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PMID:[Atrial natriuretic peptide. II. Pathophysiology and possible clinical significance. Review]. 214 57

In patients with cirrhosis of the liver sodium retention plays an important role in fluid and salt disturbances. We performed a study in 3 groups of 12 compensated and 7 decompensated cirrhotic patients and 11 controls to determine the renal, hemodynamic and hormonal effect of repeated water immersion (6 immersions in 3 weeks). In all groups immersion resulted in a marked acute natriuresis and diuresis combined with acute reduction of blood pressure. In both cirrhotic groups we found decreased salt excretion except the acute effect of immersion in comparison with controls. The natriuresis of the immersion day were in decompensated patients significantly elevated in comparison with a control day. This was not due to the acute, but the prolonged immersion effect on renal excretion. During the study the immersion effects increased in both groups of cirrhotic subjects. The controls showed decreased responses. The immersion response shall be caused at least, in part by the Atrial Natriuretic Peptide (ANP): all groups had a significant elevation of ANP during the immersion which was like the renal natriuresis prolonged in the 6th immersion in cirrhotics. A repeated water immersion may improve the natriuretic responsiveness of cirrhotics, especially those of decompensated patients.
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PMID:[Renal, hemodynamic and hormonal effects of repeated water immersion in liver cirrhosis]. 215 Nov 13

This paper describes two patients with liver cirrhosis presenting with right sided hydrothorax. The diagnosis of hepatic hydrothorax was confirmed by a radionuclide study using an intraperitoneal injection of radioactive 99mTc-tin-colloid, demonstrating the one-way transdiaphragmatic flow of fluid from the peritoneal to pleural cavities. Pleural taps, salt restriction and diuretics resulted in volume depletion and impaired renal function in the first patient. Medical therapy and a single thoracocentesis were successful in the other patient.
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PMID:Hepatic hydrothorax: report of two cases. 216 9

The onset of sodium retention in the phenobarbital and carbon tetrachloride model of cirrhosis in the rat is preceded by a linear decrease in hepatic function as measured by the aminopyrine breath test. Sodium retention occurs when liver function decreases below a critical threshold. Changes in systemic hemodynamics may be responsible for initiating the development of renal sodium retention. The objective of this study was to investigate the relationship between hepatic function and systemic and renal hemodynamics of experimental cirrhosis in rats maintained on a constant salt diet. Cirrhosis was induced in phenobarbital-treated rats by weekly administration of carbon tetrachloride. The aminopyrine breath test served as a measure of hepatic function. Three groups of animals were studied to evaluate the contribution of changes in systemic and renal hemodynamics to the onset of sodium retention: a group with sodium retention and aminopyrine breath test results just below the critical threshold, a group without sodium retention and aminopyrine breath test results just above the critical threshold and a phenobarbital-treated control group. In each group, urinary sodium excretion, renal plasma flow, glomerular filtration rate, mean arterial pressure and arterial and renal venous plasma renin activities were determined. A progressive, significant reduction in mean arterial pressure was seen, comparing controls with the other two groups. No differences in renal plasma flow were observed between the three groups, but glomerular filtration rate and filtration fraction were slightly reduced in the sodium-retaining group compared with the non-retaining group and controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal and systemic hemodynamics in experimental cirrhosis in rats: relation to hepatic function. 219 9

The onset of sodium retention in phenobarbital/carbon tetrachloride-induced cirrhosis in rats is preceded by a linear decrease in hepatic function as assessed by the aminopyrine rate constant of elimination. Sodium retention occurs when liver function decreases below a critical aminopyrine rate constant of elimination threshold of 1 min-1 x 10(-3). The objective of this study was to investigate this relationship in a different experimental model of cirrhosis in rats and to learn whether alteration of drug-metabolizing activity by hepatic enzyme induction changes the threshold for urinary sodium retention. Cirrhosis was induced in untreated and phenobarbital-treated rats by bile duct excision. Liver function, assessed by the aminopyrine breath test, and urinary sodium excretion on a constant salt diet were measured weekly for up to 4 wk. In untreated rats, the aminopyrine breath test rate constant of elimination was reduced by about 40% within 1 wk of surgery. Aminopyrine rate constant of elimination then decreased more slowly, but linearly. Urinary sodium excretion was initially unchanged, but sodium retention occurred after 2.5 wk and was maintained until the end of the experiment. Phenobarbital-treated rats had greater initial aminopyrine rate constant of elimination, but we saw a similar fall in aminopyrine rate constant of elimination of about 40% within 1 wk of bile duct excision to a value still above baseline aminopyrine rate constant of elimination of untreated controls. Aminopyrine rate constant of elimination remained at a plateau for 3.5 wk without changes in urinary sodium excretion. After 3.5 wk, a sudden decrease in aminopyrine rate constant of elimination was associated with the sudden onset of sodium retention.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phenobarbital influences the development of sodium retention in liver disease induced by bile duct ligation in the rat. 234 52

Although sodium retention is a common complication in advanced liver disease, the relationship between liver and kidney function in cirrhosis has not been well established. The objective of this study was to investigate this relationship in an experimental model of cirrhosis induced in phenobarbital-treated rats by weekly intragastric administration of carbon tetrachloride. Liver function, measured by the aminopyrine breath test, and urinary sodium excretion on a constant salt diet, were measured weekly. Administration of carbon tetrachloride led to cirrhosis, sodium retention, ascites and a reduction in liver function as measured by the amino pyrine breath test in all 15 rats surviving the first 8 wk. The time to develop sodium retention (defined as a decrease in urinary sodium excretion rate to less than 0.3 mmol/24 hr) varied from 9 to 19 wk. The aminopyrine breath test rate constant of elimination was reduced from 24 x 10(-3) min-1 +/- 2 x 10(-3) min-1 at the start of carbon tetrachloride administration by 61% +/- 10% at the time sodium retention occurred. A linear decrease was seen in aminopyrine breath test rate constant of elimination in the weeks preceding the onset of sodium retention. Sodium retention occurred when aminopyrine breath test rate contant of elimination was reduced to a critical threshold of 10 x 10(-3) +/- 1 x 10(-3) min-1, and then permitted to recover above this level by withdrawal of carbon tetrachloride. Sodium retention occurred when the aminopyrine breath test rate constant of elimination fell below the threshold; this was followed by spontaneous diuresis when aminopyrine breath test rate constant of elimination improved above 10 x 10(-3) +/- 1 x 10(-3) min-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The onset of sodium retention in experimental cirrhosis in rats is related to a critical threshold of liver function. 234 53

Bile flow may be considerably increased in human cirrhosis. The mechanism of this increase has not been established. Two mechanisms have been proposed: a) increased canalicular filtration because of sinusoidal hypertension, or b) secretion by proliferated bile ductules. To distinguish between these two possibilities, we examined the determinants of bile secretion in rats with secondary biliary cirrhosis after bile duct obstruction. Sham-operated animals served as controls. Four weeks after bile duct ligation, all animals had cirrhosis. Bile flow was significantly higher and bile salt secretion significantly lower in cirrhotic animals than in controls. Biliary bicarbonate concentration was significantly higher in cirrhotic animals than in controls. Bile-to-plasma concentration ratio of erythritol was significantly lower in cirrhotic animals than in controls, suggesting a dilution of erythritol by a secretion distal to bile canaliculi. Bile-to-plasma ratio of sucrose was not significantly different in cirrhotics and controls, suggesting that paracellular permeability was not modified. Secretin, at the dose of 3 clinical units/100 g, induced an increase of approximately 75 percent in bile flow, and 70 percent in biliary bicarbonate concentration in cirrhotics. In conclusion, bile flow was increased in biliary cirrhosis in rats. The dilution of erythritol, the increase in biliary bicarbonate concentration and the increased response to secretin strongly suggest that increased choleresis was due, at least in part, to secretion by bile ductules or ducts. These results confirm that secondary biliary cirrhosis is a good experimental model for the study of alterations of bile secretion in cirrhosis.
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PMID:[An increase of choleresis in secondary biliary cirrhosis in rats is caused by bile duct secretion]. 235 Dec 43


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