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)

Phosphodiesterase I (EC 3.1.4.1) activity was detected in normal human blood serum. The enzyme is stable at laboratory temperature for three days, but is inactivated at pH less than 7. The pH for optimum activity increases with the substrate concentration (under the conditions used, from pH 9.0 to 10.2) and, conversely, the Km increases with pH and buffer concentration. The enzyme is inhibited by ethylenediaminetetraacetate but not by phosphate (0.1 mol/liter). We developed a simple quantitative method for its determination, based on hydrolysis of the p-nitrophenyl ester of thymidine 5'-monophosphate and subsequent measurement of the liberated p-nitrophenol at 400 nm in NaOH (0.1 mol/liter). Normal values (mean +/- 2 SD) were determined to be 33 +/- 6.4 U/liter. Preliminary studies indicate that phosphodiesterase I activity is greater than normal in serum of patients with necrotic changes in the liver or kidney or in cases of breast cancer, but not in that of patients with myocardial infarction, bone cancer, lung cancer, or chronic liver cirrhosis.
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PMID:Determination of phosphodiesterase I activity in human blood serum. 16 91

Theophylline and its derivatives, such as aminophylline, have an established role as bronchodilators, although their mode of action in man is not clear. There is circumstantial evidence that therapeutic doses of theophylline may have a phosphodiesterase inhibiting effect, thus potentiating the effects of cyclic AMP. However, it remains to be established whether this is the primary mode of action of theophylline at the biochemical level. The pathways of theophylline metabolism have been clarified, although most of the enzymes involved have not been characterized. Hepatic microsomal enzyme induction by polycyclic hydrocarbons will increase the rate of theophylline elimination. There are a number of factors which influence theophylline clearance in adults, which is known to be highly variable. These factors include obesity, smoking habit, diet and the presence of such diseases as hepatic cirrhosis, acute pulmonary oedema, cor pulmonale and viral respiratory infection. There is a good correlation between plasma theophylline level and bronchodilator effect. This can be demonstrated at plasma levels as low as 5 microgram/ml, although optimal levels are usually greater than 10 microgram/ml. Unacceptable toxicity usually occurs in association with plasma levels greater than 20 microgram/ml. The maintenance of adequate plasma theophylline levels by the use of a sustained-release aminophylline tablet is discussed.
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PMID:Theophylline: biochemical pharmacology and pharmacokinetics. 22 Jan 19

The clinical usefulness of serum 5'-nucleotide phosphodiesterase isozyme-V (5'-NPD-V) assay as a serological marker for hepatocellular carcinoma was evaluated. Serum levels of 5'-NPD-V were measured by polyacrylamide gel electrophoresis in 536 Japanese patients with various diseases, including 120 patients with hepatocellular carcinoma. Icteric serum was not an indicator for the measurement of this isozyme, because jaundice gave a non-specific false-positive reaction. In 99 cases of hepatocellular carcinoma without jaundice, 73 (74%) had positive 5'-NPD-V and 24 (24%) showed levels greater than (+ +). The diagnostic value of this isozyme for hepatocellular carcinoma was relatively high, especially in patients with low or negative AFP levels. Diagnostic application for serum 5'-NPD-V assay to small liver tumors was limited. 5'-NPD-V showed false-positive results even in certain cases of benign liver diseases such as chronic hepatitis and liver cirrhosis, but cases with positivities stronger than (+ +) were few. Moreover, the test might be useful for the prediction of liver metastasis in cancer patients, since positive rates were significantly higher in cases with liver metastasis than in those in the non-liver metastasis group.
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PMID:5'-Nucleotide phosphodiesterase isozyme-V in hepatocellular carcinoma and other liver diseases. 170 10

A new in vitro bleeding time (BT) device was applied to various surgical patients. After setting the optimal assay condition, the normal in vitro bleeding time (T2) and volume (V2) were obtained from healthy volunteers, being 114.7 secs +/- 25.8 (SD) and 272.2 microliter +/- 69.1 (SD), respectively. When the T2 was below 210 secs, the platelet count was inversely proportional to the T2 and V2 of the in vitro BT with p less than 0.01. The value of the in vitro BT was not affected by heparin. Agents, which modify platelet functions, such as PGI2, DN9693 (an inhibitor of phosphodiesterase) and aspirin, prolonged the in vitro BT (T2, V2) dose-dependently. Administration of aspirin (660 mg) to volunteers prolonged the T2 from 108 to over 300 secs and the V2 from 253 to over 600 microliter but ticlopidine (500 mg/day for 3 days) had no effect. In 8 patients with liver cirrhosis who underwent hepatectomy, one patient with a prolonged T2 (260 secs) and a normal skin BT bled postoperatively, however, 3 patients with a prolonged skin BT (greater than 15 min) and a normal T2 had no hemorrhagic complications. From these observations it was concluded that in vitro BT is a convenient and useful tool to examine primary hemostasis or platelet function.
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PMID:Clinical application of a new in vitro bleeding time device on surgical patients. 284 75

The levels of 5'-nucleotide phosphodiesterase isoenzymes (5'-NPD; EC 3.1.4.1) in sera of 54 healthy donors and 201 inpatients were measured. Isozymes were separated electrophoretically and designated as 5'-NPD-0, -I, -II, -III, -IV and -V in the reverse order of their electrophoretic mobility. In healthy donors all isozymes except 5'-NPD-V were detectable. In pathological sera isozymes 0 to V were elevated in 26.0%, 20.5%, 14.0%, 30.5%, 7.0% and 15.0% of the cases, respectively. Decreased values were found in 6-7%, with the exception of 5'-NPD-IV showing decreased activities in 23.5% of the patients. This average distribution pattern was found in many disorders. However, in diseases of the liver and the pancreas a remarkable accumulation of cases with elevated levels of all isozymes, except 5'-NPD-IV, was observed. All isozymes, except 5'-NPD-IV, showed many significant correlations with other laboratory parameters indicating liver disease. Isozyme IV was not related to these parameters but exhibited a strong correlation with serum albumin. 5'-NPD-II was unproportionally often increased in patients with liver cirrhosis and was the only isozyme with on the average higher levels in women than in men.
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PMID:Levels of 5'-nucleotide phosphodiesterase isoenzymes in normal and pathological sera. 285 13

An ELISA has been developed for detection of auto-antibodies against calmodulin. There was a significantly increased frequency (63.1%) of autoantibodies against calmodulin in 103 patients with chronic liver diseases as compared to that (30%) of patients with systemic lupus erythematosus and to that (6.9%) of normal subjects (p less than 0.01). IgG autoantibodies against calmodulin were detected in the patients with acute hepatitis (37.9%), chronic liver disease (45.6%) and also in the patients with systemic lupus erythematosus (30%). IgM autoantibodies against calmodulin were frequently found in patients with liver cirrhosis (52.2%), primary biliary cirrhosis (50%) and autoimmune chronic active hepatitis (38.7%), but rarely in patients with acute hepatitis (13.8%), chronic persistent hepatitis (9.5%) and systemic lupus erythematosus (0%). IgA autoantibodies against calmodulin were frequently found in liver cirrhosis (33.3%), primary biliary cirrhosis (42.9%) and autoimmune chronic active hepatitis (53.6%), but rarely in chronic persistent hepatitis (15.8%), chronic active hepatitis (14.3%) and systemic lupus erythematosus (0%). The occurrences of autoantibodies against calmodulin correlated neither with those of antismooth muscle antibody, antinuclear antibody and antimitochondrial antibody, nor with serum IgG concentrations. Autoantibodies against calmodulin did not cross-react with troponin, myosin light chain, calf thymus DNA and actin. The titer of autoantibodies against calmodulin was decreased by absorption of serum with calmodulin and the liver plasma membrane fraction. The immunoblotting experiment revealed the binding of autoantibodies against calmodulin to calmodulin. IgG fraction from a patient with autoimmune chronic active hepatitis inhibited the activation of phosphodiesterase by calmodulin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anticalmodulin autoantibody in liver diseases: a new antibody against a cytoskeleton-related protein. 355 8

2,131 coded sera were obtained and tested according to the new 5'-NPDase-V isozyme test. On decoding, 99/126 (79%) samples of primary hepatoma, from the United States and other countries, were positive. In the U. S. group, 51/58 (88%) were positive, 23/58 (40%) had AFP higher than 20 ng/ml. In the non-U. S. group, 48/68 (71%) were positive for 5'-NPDase-V, as compared with AFP elevation in 45/68 (66%). 236/268 (88%) cases of cancer with known liver metastases were positive for 5'-NPDase-V. Of 1,040 cancer patients without liver scan or biopsy evidence of metastasis, 316 were positive. In a follow-up of this group of 316 cases, 109 underlying liver metastases were demonstrated by repeat scan or at autopsy within 3--6 months. All 166 sera from normal healthy persons were negative for 5'-NADase-V. Based on this large panel, 5'-NPDase-V test is a sensitive and an important diagnostic aid for cancer patients, both as an early predictor for liver metastases, and a useful marker for primary hepatoma when no other primary sites are found and when there is no evidence of severe chronic liver disease such as cirrhosis.
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PMID:Serum 5'--nucleotide phosphodiesterase isozyme--V test for human liver cancer. 615 48

Resistance to the natriuretic action of atrial natriuretic peptide (ANP) is a hallmark of states of pathological sodium retention including congestive heart failure, cirrhosis of the liver, and nephrotic syndrome. A variety of mechanisms including reduced delivery of filtrate to ANP-sensitive sites in the inner medullary collecting duct and diminished receptor density in this tubular segment have been offered to account for this resistance. Recent studies in experimental nephrotic syndrome and in liver disease produced by ligation of the common bile duct in rats suggest that increased activity of cyclic guanosine 3',5'-monophosphate (cGMP) phosphodiesterase may be an important mediator of renal resistance to ANP. Such increased enzyme activity rapidly catabolizes the second messenger cGMP, normally formed when ANP interacts with its biologically active natriuretic peptide. A receptors, thereby leading to blunted ANP responsiveness. This increased phosphodiesterase activity offers a novel approach to the management of clinical conditions associated with sodium retention and edema formation.
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PMID:Phosphodiesterases (PDEs) hydrolyze the 3' phosphoester bond of the purine 3',5'-cyclic monophosphates, cAMP and cGMP. 876 Feb 35

Resistance to the natriuretic action of atrial natriuretic peptide (ANP) is a hallmark of states of pathological sodium retention including congestive heart failure, cirrhosis of the liver, and nephrotic syndrome. A variety of mechanisms including reduced delivery of filtrate to ANP-sensitive sites in the inner medullary collecting duct and diminished receptor density in this tubular segment have been offered to account for this resistance. Recent studies in experimental nephrotic syndrome and in liver disease produced by ligation of the common bile duct in rats suggest that increased activity of cyclic guanosine 3',5'-monophosphate (cGMP) phosphodiesterase may be an important mediator of renal resistance to ANP. Such increased enzyme activity rapidly catabolizes the second messenger cGMP, normally formed when ANP interacts with its biologically active natriuretic peptide A receptors, thereby leading to blunted ANP responsiveness. This increased phosphodiesterase activity offers a novel approach to the management of clinical conditions associated with sodium retention and edema formation.
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PMID:Phosphodiesterase activity as a mediator of renal resistance to ANP in pathological salt retention. 876 Feb 36

A possible defect of guanosine 3'-5'-cyclic monophosphate (cGMP) content in the renal tissue caused by an increased activity of cGMP phosphodiesterase (PDE) has, so far, not been evaluated in the pathogenesis of renal resistance to endogenous natriuretic peptides (ENP) in cirrhosis with ascites. To test this hypothesis the activity of cGMP-PDE and the concentration of cGMP were evaluated in vitro in the renal tissue of 10 control rats and 10 cirrhotic rats with ascites before and after the intravenous (IV) administration of Zaprinast (Sigma, St. Louis, MO), a specific cGMP-PDE inhibitor (30 microgram/kg/min). Moreover, the effects of the intravenous administration of Zaprinast (15 microgram/kg/min and 30 microgram/kg/min) on renal plasma flow (RPF), glomerular filtration rate (GFR), and urinary sodium excretion (U(Na)V) were evaluated in 10 conscious control rats and 10 conscious cirrhotic rats with ascites. The effects of Zaprinast on plasma renin activity (PRA) was also evaluated in 10 control rats and in 10 cirrhotic rats with ascites. Finally, the effect of Zaprinast on RPF, GFR, and U(Na)V were evaluated in 10 cirrhotic rats after the IV administration of the ENP-receptor antagonist, HS-142-1. The renal content of cGMP was reduced in cirrhotic rats because of increased activity of cGMP-PDE. Zaprinast inhibited cGMP-PDE activity and increased the renal content of cGMP in these animals. The inhibition of cGMP-PDE was associated with an increase in RPF, GFR, and U(Na)V and a reduction in PRA. HS-142-1 prevented any renal effect of Zaprinast in cirrhotic rats. In conclusion, an increased activity of the cGMP-PDE in renal tissue contributes to the renal resistance to ENP in cirrhosis with ascites.
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PMID:Increased activity of guanosine 3'-5'-cyclic monophosphate phosphodiesterase in the renal tissue of cirrhotic rats with ascites. 1065 50


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