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)

12 g of albumin are synthesized daily by the bound polyribosomes of all human liver cells together, corresponding to 10% of the intravascular albumin mass. The cell is producing a precursor albumin. During secretion albumin is liberated by splitting of a small peptide. Only 40% of the total body albumin is located intravascularly. 12g of albumin are degraded or excreted daily, 30% of it by the liver, the kidneys and the gastrointestinal tract. The main site of albumin catabolism is unknown. Albumin with a half-life of about 20 days is degraded at a constant fractional catabolic rate. The absolute rate of degradation varies depending on the plasma content. This mechanism allows an effective regulation of the serum albumin level. The fractional catabolic rate, however, is not completely fixed. It is slowly reduced if the serum albumin content is markedly reduced as in protein deficiency, the blind loop syndrome, cirrhosis, nephrosis, and diseases of the gastrointestinal tract. Infusion of albumin increases the fractional catabolic rate slowly. This must be taken in consideration substitution albumin in chronic diseases. The shift from the extravascular to the intravascular compartment is a short-term regulatory mechanism. The regulation of synthesis and degradation are independent from each other. The molecular mechanism of regulation of synthesis and degradation are unknown, partially due to inadequate methods.
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PMID:[The regulation of serum albumin in physiological and pathological conditions (author's transl)]. 87 Jul 44

Common features of chronic alcoholic liver disease are progressive hypoalbuminemia and liver fibrosis. The molecular mechanisms which account for these effects are still controversial. Therefore, in the present study we evaluated albumin and collagen gene expression in livers of alcohol abusers and patients with viral-induced liver disease. Albumin and pro-alpha 1 (I) collagen mRNA levels were determined in 30 patients who underwent diagnostic liver biopsy. Of 14 alcoholics, 7 had alcoholic hepatitis alone, while the other 7 had cirrhosis plus alcoholic hepatitis. Of 16 non-alcoholic patients with chronic viral infection, 6 had chronic active hepatitis and 10 cirrhosis plus chronic active hepatitis. Total RNA was extracted from a portion of each biopsy, hybridized with a human albumin or collagen cDNA clone and compared to 2 normal surgical specimens which served as controls. The Northern hybridization studies revealed that: despite the presence of inflammation and fibrosis, the albumin mRNA levels of alcoholics were similar to normal controls; these alcoholics had significantly higher levels of albumin mRNA than did patients with similar histological stages of disease due to viral infection; and all the categories of patients had markedly increased procollagen mRNA levels when compared to controls. Given these results it is tempting to speculate that alcohol may actually increase albumin mRNA content in man as it does in animals. Furthermore, the increased procollagen mRNA levels in fibrotic livers suggest that an increase in collagen synthesis may be a significant factor in the pathogenesis of hepatic fibrosis.
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PMID:Albumin and procollagen type I gene regulation in alcohol and viral-induced human liver disease. 167 41

Liver scintigraphy was performed using a newly developed radiopharmaceutical, Tc-99m-DTPA-Galactosyl-Human-Serum-Albumin (Tc-99m-GSA), which binds specifically to the receptors on the hepatic cell surface, in 15 patients with chronic liver diseases. The scintigraphy was evaluated qualitatively and quantitatively, and the results were compared with those obtained from the Tc-99m-PMT or Tc-99m-sn-phytate scintigraphy, and the liver function tests. The Tc-99m-GSA scintigraphy showed clear liver images in chronic hepatitis. However, in liver cirrhosis, the liver images was not clear and the cardiac images still existed 40 minutes after administration of Tc-99m-GSA, suggesting that the image quality of the Tc-99m-GSA scintigrams may be inferior to that of Tc-99m-sn-phytate or Tc-99m-PMT in some cases of severe liver dysfunction. The time-activity curves of the heart and liver were analyzed by non-linear regression analysis. The clearance rate from plasma (Kd) were obtained from the time-activity curve of the heart, and the hepatic uptake rate (Ku), hepatic excretion rate (Ke) and peak time of hepatic uptake-excretion curve (PT) were obtained from the time-activity curve of the liver. Kd, Ku and PT values were more significantly decreased or prolonged in the patients with liver cirrhosis than those in the patients with chronic hepatitis. Kd, Ku and PT values had positive correlations with the result of the serum liver function tests, ICG-R15 and ICG-K. Ku and PT values had also correlations with the histological degrees of hepatic fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Evaluation of usefulness of Tc-99m-GSA liver scintigraphy in chronic liver diseases]. 177 Jun 48

The expression of albumin mRNA in human liver samples was investigated in order to understand the molecular mechanism of albumin gene expression in various liver diseases. Albumin mRNA in acute hepatic failure and decompensated liver cirrhosis was reduced significantly compared to normal control liver (P less than 0.05). Serum albumin concentration is closely correlated with albumin mRNA content (r = 0.895, P less than 0.01). These data suggest that albumin concentration is mainly regulated at albumin mRNA level in the liver despite the presence of other regulatory mechanisms and that expression of albumin mRNA level is correlated with disease severity. But in several cases there was a discrepancy between albumin mRNA level and severity of liver disease, so further investigation of the regulatory factors of albumin gene expression should be performed.
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PMID:Albumin mRNA expression in human liver diseases and its correlation to serum albumin concentration. 191 56

Common features of chronic alcoholic liver disease are progressive hypoalbuminemia and a spectrum of liver fibrosis. The molecular mechanisms that account for these effects are still the subject of controversy. Therefore, in the present study we evaluated albumin and collagen gene expression in livers of alcohol abusers and patients with virus-induced liver disease. Albumin and pro alpha 1(I) collagen messenger RNA levels were determined in 30 patients who underwent diagnostic liver biopsy. Of 14 alcoholics, 7 had alcoholic hepatitis alone and the other 7 had cirrhosis plus alcoholic hepatitis. Of 16 nonalcoholic patients with chronic viral infection, 6 had chronic active hepatitis and 10 had cirrhosis plus chronic active hepatitis. Total RNA was extracted from a portion of each biopsy specimen, hybridized with a human albumin or collagen complementary DNA clone, and compared with 2 normal surgical specimens, which served as controls. The Northern hybridization studies showed that (a) despite the presence of inflammation and fibrosis, the albumin messenger RNA levels of alcoholics were similar to those of the controls; (b) these alcoholics had significantly higher levels of albumin messenger RNA than did patients with similar histological levels of disease due to viral infection; and (c) all the categories of patients had markedly increased procollagen messenger RNA levels compared with controls. Given these results it is tempting to speculate that alcohol may actually increase albumin messenger RNA content in humans as it does in animals. Furthermore, the increased procollagen messenger RNA levels in fibrotic livers suggest that an increase in collagen syntheses may be a significant factor in the pathogenesis of hepatic fibrosis.
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PMID:Albumin and collagen gene regulation in alcohol- and virus-induced human liver disease. 229 78

Plasma levels of atrial natriuretic peptide (ANP), aldosterone (PA), vasopressin (AVP), and the plasma renin activity (PRA) were examined in 15 vascularly decompensated patients suffering from liver cirrhosis, before and after administration of albumin and after a subsequent administration of furosemide. The initial ANP level was lower in 9 patients (group "A") and higher in 6 patients (group "B") than in healthy controls (Group "A": 19.5 +/- 3.0 fmol/ml; group "B": 36.7 +/- 3.9 fmol/ml; control: 25.8 +/- 2.4 fmol/ml). The initial PRA (4.4 +/- 1.0 ng AngI/ml/h) and AVP (8.5 +/- 1.5 pg/ml) activity in group "A" increased significantly compared to group "B" (PRA: 0.44 +/- 0.09; AVP: 4.1 +/- 0.5), indicating an intravascular volume depletion in group "A". Albumin infusion raised the urine and sodium excretion and the plasma concentration of ANP in group "A" but lowered in plasma levels of renin and vasopressin. The same parameters were not changed by albumin in group "B". Furosemide equally raised the urine flow rate and sodium excretion in both groups. Plasma ANP level depends on the intravascular volume, and the secondary change in its plasma concentration plays a considerable role in the retention of fluid and electrolytes in patients with cirrhosis. The increased intravascular volume in these patients depletes the fluid and electrolyte retention via the increase in ANP level.
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PMID:Alterations of vasoconstrictor and sodium-regulating hormone systems in vascularly decompensated liver cirrhosis. 297 Jun 21

Bile acids and other bile constituents were determined in serum and ascites from eight patients with liver cirrhosis and in ascites secondary to malignancy in six patients. In cirrhotic ascites, total bile acid levels averaged 53% of the serum levels. A positive correlation was evident between ascites and serum levels for both cholic and chenodeoxycholic acid. For cholic acid, the ascites to serum ratio was higher in all patients compared with the corresponding ratio for chenodeoxycholic acid. The ascites to serum ratios for glycine, taurine and sulphate conjugates were similar, no tendency being shown by any of the conjugates to leak more easily into ascites. The high levels of bile acids in cirrhotic ascites suggests that the abdominal cavity harbours a fraction of the bile acid pool, which should be taken into account when studying bile acid turnover in liver cirrhosis. Bilirubin levels in cirrhotic ascites averaged 24% of the serum values. A positive correlation between ascites and serum levels for unconjugated bilirubin was recorded, whereas the occurrence of bilirubin conjugates in ascites was variable. Albumin levels in cirrhotic ascites were 25% of the serum levels. The ascites to serum ratios for other proteins such as IgG, IgA and IgM and also cholesterol and phospholipids were lower than that for albumin. In malignant ascites, a pattern different from that in liver cirrhosis was seen, low bile acid levels being found. No difference between bilirubin levels was observed, while albumin and cholesterol levels were higher in malignant ascites, with no overlap between the patient groups. These results indicate that the complex mechanisms of ascites formation result in variable levels of bile constituents in ascitic fluid, which are further dependent on the underlying disease.
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PMID:Bile constituents in ascitic fluid. 321 57

This paper critically examines the usefulness of serum albumin measurement in the light of current laboratory practice and knowledge of the pathophysiology of albumin metabolism. The main conclusions and recommendations are as follows: (i) Albumin measurement forms a limited, but useful part of the investigation of liver disease; a normal serum albumin concentration makes the diagnosis of cirrhosis unlikely, while a low level in viral hepatitis suggests either severe hepatocellular damage or other complications. (ii) Albumin measurement is essential in selecting patients for, and in determining the amount and frequency of, albumin replacement. (iii) Serum albumin concentration provides a useful indication of prognosis in myeloma. (iv) In the long-term management of patients undergoing enteral or parenteral nutrition, serum albumin concentration is one of several parameters which, together, are useful in predicting the outcome of treatment. (v) The serum albumin concentration may provide a clue to the aetiology of unexplained oedema. (vi) Serum albumin measurement is useful in indicating the level of ionised calcium and of unbound unconjugated bilirubin.
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PMID:When is serum albumin worth measuring? 332 60

Recent advances in techniques to determine free drug concentrations have lead to a substantial increase in the monitoring of this parameter in clinical practice. The majority of drug binding to macromolecules in serum can be accounted for by association with albumin and alpha 1-acid glycoprotein. Albumin is the primary binding protein for acidic drugs, while binding to alpha 1-acid glycoprotein is more commonly observed with basic lipophilic agents. Alterations in the concentrations of either of these macromolecules can result in significant changes in free fraction. Diseases such as cirrhosis, nephrotic syndrome and malnourishment can result in hypoalbuminaemia. Burn injury, cancer, chronic pain syndrome, myocardial infarction, inflammatory diseases and trauma are all associated with elevations in the concentration of alpha 1-acid glycoprotein. Treatment with a number of drugs has also been shown to increase alpha 1-acid glycoprotein serum concentrations. A wide variety of biological fluids have been examined for their ability to provide an estimation of free drug concentration at receptor sites. The most useful fluid for estimating free drug concentrations appears to be plasma or serum, with subsequent treatment of the sample to separate free and bound drug by an appropriate technique. The two most widely used methods are equilibrium dialysis and ultrafiltration. Of these two, ultrafiltration has the greatest utility clinically because it is rapid and relatively simple. The major difficulty associated with this method involves the binding of drug to the ultrafilters, but significant progress has been made in solving this problem. Several authors have endorsed the routine use of free drug concentration monitoring. Data examining the clinical usefulness of free drug concentration monitoring for phenytoin, carbamazepine, valproic acid, disopyramide and lignocaine (lidocaine) are reviewed. While available evidence suggests that free concentrations may correlate with clinical effects better than total drug concentrations, there are insufficient data to justify the recommendation of the routine use of free drug concentration monitoring for any of these agents at present.
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PMID:Free drug concentration monitoring in clinical practice. Rationale and current status. 354 37

A method for the simultaneous measurement of gastrointestinal protein loss and total albumin turnover entailing the use of a combination of (125)iodine- and (51)chromium-labeled albumin is described. Albumin turnover was calculated by the measurement of albumin-(125)I plasma decay and cumulative urinary excretion, and the results obtained agreed closely with previous studies utilizing albumin-(131)I. Gastrointestinal catabolism was calculated from the rate of fecal excretion of (51)Cr and the specific activity of plasma albumin-(51)Cr, and these data were related to the calculated albumin turnover results. During the period of 6-14 days after administration, the ratio of specific activties of albumin-(125)I and -(51)Cr in plasma and in extravascular spaces or gastric and biliary secretions remained almost identical. Fecal excretion of (51)Cr was also quite stable at this time. In six normal subjects gastrointestinal catabolism accounted for less than 10% of total albumin catabolism. Excessive gastrointestinal protein losses did not contribute to the low serum albumin in three patients with cirrhosis or in two adults with the nephrotic syndrome. Multiple mechanisms leading to hypoalbuminemia were demonstrated in other subjects with a variety of gastrointestinal disorders.
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PMID:Use of 125-I- and 51-Cr-labeled albumin for the measurement of gastrointestinal and total albumin catabolism. 563 Apr 19


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