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 aim of this study was to characterize acidic glycosaminoglycan components in normal human liver and in alcoholic cirrhosis, and to determine whether the proportions of individual glycosaminoglycans change with advancing cirrhosis. Acidic glycosaminoglycans are components of extracellular matrices and consist of repeating disaccharides of hexosamine and hexuronic acid with molecular weights ranging from 5 X 10(3) to 5 X 10(4), except for hyaluronic acid, whose molecular weight ranges from 3 X 10(4) to 1.6 X 10(6). The acidic glycosaminoglycan components in normal liver and at different stages of liver cirrhosis were found to be polydisperse as to the molecular weight and the degree of sulfation. The increased content of glycosaminoglycans with advancing liver cirrhosis was related to those of heparan sulfate and dermatan sulfate components. Heparan sulfates were the most prominent components of smaller molecular weight fractions. In the normal state, moderate amounts of dermatan sulfate and the oversulfated isomer were present in intermediate molecular weight fractions, but increasing amounts of the components shifted to higher molecular weight fractions with advancing cirrhosis. A small amount of hyaluronic acid was found in higher molecular weight fractions and the amount increased at the initial stage as a reversible phenomenon. The possible roles of hepatic glycosaminoglycan components in the process of fibrosis are discussed.
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PMID:Polydispersity of acidic glycosaminoglycan components in human liver and the changes at different stages in liver cirrhosis. 405 17

We have assessed the clinical utility of a radioimmunoassay for alpha-fetoprotein (AFP). The method, which relies on ammonium sulfate precipitation for the separation of "bound" and "free" radiolabeled antigen, can be completed in one working day. The assay is specific for AFP, has a sensitivity of < 10 ng/ml, and has intra- and inter-assay precision of 5--8% and 9--11%, respectively. We have conducted a three-year study of 472 pregnancies in which physicians wished to detect neural tube defects, and of 400 non-pregnant patients to assess the value of serum AFP as a marker for certain benign and malignant diseases. Six of 6 fetal open neural-tube defects (NTD's) and 3 of 3 intrauterine fetal deaths were correctly identified by their association with marked AFP elevations in both maternal serum and amniotic fluid. Thirty non-pregnant patients were found to have AFP elevations greater than 20 ng/ml. Malignancies associated with these elevations were hepatoma, germ cell tumors, Wilms' tumor, and carcinoma of unknown origin. Carcinoma metastatic to the liver was not associated with AFP elevations. In AFP-associated tumors we found serial measurements of serum AFP to be of value in assessing therapeutic response. Benign diseases associated with AFP elevations included neonatal hepatitis, viral hepatitis, fulminant toxic hepatitis, and cryptogenic cirrhosis.
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PMID:alpha-Fetoprotein in the routine clinical laboratory: evaluation of a simple radioimmunoassay and review of current concepts in its clinical application. 615 81

The efficacy of administration of oral paromomycin sulfate on serum albumin and gamma-globulin levels was studied in cirrhotic patients. After an observation period of 3 months, paromomycin sulfate at 2.0 g per day or a placebo was administered for 6 months, and changes in serum albumin and in gamma-globulin levels were examined every three months. Out of 16 cirrhotic patients treated with paromomycin, 11 (68.8%) showed significant increases in serum albumin compared with one out of 16 in the placebo group. Concerning gamma-globulin, seven (43.8%) patients in the paromomycin group showed significant decreases compared with one in the placebo group. In addition, among the 11 cirrhotics whose endotoxemia decreased after paromomycin administration, eight (72.7%) showed significant increases in albumin level. It was suggested that paromomycin improves the serum albumin and gamma-globulin levels in cirrhosis through the alleviation of endotoxemia caused by intestinal bacteria.
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PMID:Effect of long-term administration of paromomycin sulfate on the level of serum albumin and gamma-globulin in human cirrhosis. 620 39

We isolated galactosyltransferase (EC 2.4.1.22) from pleural effusions of a lung cancer patient and a patient with cirrhosis by precipitation with ammonium sulfate, followed by gel filtration on Sepharose 6B, and affinity chromatography on columns of alpha-lactalbumin-agarose and protein A-Sepharose. By this procedure the enzyme from both sources was purified 40 000-fold with approximate yields of 37% and 60%, respectively, and did not contain immunoglobulin. Electrophoresis on polyacrylamide gel of the enzyme from the cancer patient (slower moving) and from the non-cancer patient (faster moving) gave one sharp band for each. Their respective relative molecular masses, 74 131 and 107 151, were estimated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and gel filtration, respectively. The isoenzymes were active between pH 5 and 8, most active at 7, and showed no activity below pH 4 or above pH 9. Activity was greatest at temperatures between 37 and 40 degrees C. At 30 degrees C or 50 degrees C the activity was more than halved, and was lost completely above 60 degrees C. The isoenzymes had an absolute requirement for Mn2+. Omitting the surfactant Triton X-100 from the buffer resulted in considerable loss in activity of both isoenzymes. Glucose can be used as an acceptor for these isoenzymes if alpha-lactalbumin is present in the assay mixture. These isoenzymes had different Km values for UDP-galactose, N-acetylglucosamine, and Mn2+.
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PMID:Isolation and characterization of cancer-associated galactosyltransferase isoenzyme. 643 1

Acidic glycosaminoglycan (AGAG) components in normal human liver and at different stages of liver cirrhosis were studied at the constitutional disaccharide level by enzymatic assay methods. The AGAG content in human cirrhotic liver was 5-6 times that in the normal state. The most predominant AGAG components in normal human liver tissue were heparan sulfates (HS) which accounting for 63% of the total AGAG, followed by a moderate amount of dermatan sulfate (DS) and small amounts of chondroitin sulfate isomers and hyaluronic acid (HA). In addition, the oversulfated DS detected in human liver. The increase in both HS and DS content reflects an increase in total AGAG with advancing liver cirrhosis. The ratio of non-sulfated AGAG, HA plus chondroitin, to DS plus its oversulfated isomer was 0.24 in the normal state but it increased to 0.80 at the early stage of liver cirrhosis. However, the ratio decreased to 0.36 and 0.21 at the typical and advanced stages of liver cirrhosis, respectively, with progress in the fibrotic process.
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PMID:Changes in acidic glycosaminoglycan components at different stages of human liver cirrhosis. 644 Aug 47

It has been demonstrated that intragastric administration of cysteine hydrochloride in a dose of 50 mg/kg and sodium sulfate in a dose of 25 mg/kg with reference to sulfate ion reduced the circulatory disturbances, dystrophic and sclerotic changes in the rat liver caused by intragastric administration of yellow phosphorus in a dose of 1 mg/kg. Administration of the drugs interfered with the development of liver cirrhosis, stimulated regeneration, raised the adaptive abilities of hepatocytes. Cysteine protected hepatocyte mitochondria from phosphorus and activated their function. Meanwhile sulfate ion favoured glycogen accumulation in the cytoplasm of hepatocytes; cysteine hydrochloride and sulfate ion increased the content of total protein and glycogen in the liver and exerted an activating and normalizing effect on the enzymes of fatty, and carbohydrate metabolism, oxidative and energy processes.
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PMID:[Effect of cysteine hydrochloride and sulfate ion on morphological changes in the liver during chronic poisoning with yellow phosphorus]. 646 13

An assay measuring the thrombin inactivating effect of human plasma in the presence of dermatan sulfate (DS) is described. Test plasma, diluted 1/50, is incubated with human thrombin in the presence of DS. Remaining thrombin is determined with chromogenic substrate 2AcOH . H-D-CHG-Ala-Arg-pNA. Three dilutions of reference plasma suffice and the standard curve is linear. Antithrombin III (AT) exerts a small (3-8%) effect in the assay. When test plasma contains heparin above 0.05 U/ml, this unspecific effect of AT increases, but it may be abolished by antibodies against AT. In a normal material (n = 50), the SD of DS cofactor activity was greater (15%) than that of AT (8.7%). DS cofactor was normal in hereditary AT deficiency and in 15 patients with deep venous thrombosis. In liver cirrhosis and in DIC, both inhibitors were markedly depressed, to similar degrees (r = 0.84).
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PMID:Assay of dermatan sulfate cofactor (heparin cofactor II) activity in human plasma. 654 86

The knowledge about the pharmacokinetics of triamterene (TA) was limited until recently. The metabolic pathway of TA is the formation of p-hydroxytriamterene (OH-TA), which is subsequently conjugated with active sulfate to form p-hydroxytriamterene sulfuric acid ester (OH-TA-ester). The phase-II-metabolite is surprisingly pharmacologically active. TA and its metabolites were measured concomitantly by a specific and sensitive tlc-method. The i.v. kinetics of TA were determined after application of a newly developed lactic acid solution of the drug. Comparing these data with results after oral application of TA the bioavailability of TA was 52% and the extent of absorption 83%. The bioavailability of different dosage forms was correlated with in vitro-tests. In liver disease the pharmacokinetics of TA are markedly altered. While in cirrhosis the hydroxylation of TA was decreased, the biliary excretion of this agent was strongly reduced in hepatitis. In renal disease the excretion of TA and OH-TA-ester was reduced proportional to the reduction of endogenous creatinine clearance. In older patients the elimination of TA was impaired.
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PMID:[Pharmacokinetics of triamterene in healthy subjects and patients with liver and kidney function disorders]. 663 29

Bile acid glucuronides in the serum in various hepatobiliary diseases (36 cases) were quantitated by mass fragmentography and their clinical significance was discussed. Serum was added to defined amounts of deuterium-labeled bile acids and their glucuronide and sulfate derivatives, and the bile acids were separated into unconjugated, glucuronidated and sulfated groups after enzymatic cleavage of amide bonds. The liberated bile acids were quantitated by mass fragmentography. Bile acid glucuronides comprised about 7-8% of the total bile acids in the serum of various patients. Chenodeoxycholic acid was the major glucuronidated bile acid while cholic acid was mostly unconjugated. Lithocholic acid was almost all either sulfated or glucuronidated. In patients with obstructive jaundice, glucuronidated bile acids also comprised about 5%, although their absolute amounts were increased. In patients with liver cirrhosis, bile acid glucuronides were decreased, especially in decompensated cases, possibly as a result of hepatocellular dysfunction.
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PMID:Serum concentrations of bile acid glucuronides in hepatobiliary diseases. 665 18

Triamterene is extensively metabolized by the liver and undergoes important presystemic elimination in normal subjects after oral doses. We examined triamterene disposition in eight healthy controls and seven patients with cirrhosis and ascites. A specific and sensitive HPLC assay was used to measure concentrations of triamterene and of its major metabolite p-hydroxy-triamterene sulfate (OH-T-S). Apparent oral clearance of triamterene in controls averaged 1617 +/- 219 ml/min. Plasma concentration of OH-T-S was 7.2 +/- 1.1 times that of the parent compound (estimated by the ratio AUCOH -T-S/ AUCtriamterene ). Urinary recovery of OH-T-S accounted for 45% of the triamterene dose. There was 92% reduction in apparent oral clearance of triamterene (134 +/- 42 ml/min) in patients with cirrhosis. The ratio AUCOH -T-S/ AUCtriamterene fell to 0.55 +/- 0.2, and urinary recovery of OH-T-S accounted for only 15% of the dose. These changes in triamterene kinetics in patients with cirrhosis resulted in prolongation of its natriuretic effect, which lasted for up to 48 hr, whereas it was only 8 hr in the controls. These observations reinforce the concept that cirrhosis is associated with a markedly impaired disposition of drugs that have a large first-pass effect.
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PMID:Triamterene kinetics and dynamics in cirrhosis. 673 36


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