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)

Thrombomodulin (TM) is a constituent glycoprotein of endothelial cell membrane, and soluble TM is present also in plasma and urine. It was revealed by experiments using cultured HUVEC in vitro that TM is released from endothelial cell membrane not with monensin, thrombin, fibroblast growth factor, interleukin-1 or endotoxin, but with H2O2 or endotoxin-treated granulocytes. And the release was suppressed by the coexistence of gabexate mesilate or superoxide dismutase. It was suggested that soluble TM was released from endothelial cell membrane by its injury and digested to multiple molecular forms by endogenous and granulocytic protease(s). TM level in circulation is increased in cases of SLE, MCLS, diabetic angiopathy. It was increased in cases of overt DIC and decreased to the normal level when the patient was recovered from DIC. TM level in circulation was also increased in cases of decompensated liver cirrhosis and markedly in cases of renal insufficiency. It was concluded that plasma TM is a parameter reflecting endothelial injury due to inflammation or metabolic disorders of vascular system. But the interpretation of increased plasma TM was difficult when renal insufficiency was complicated.
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PMID:[Soluble thrombomodulin: a specific parameter of endothelial injury]. 185 Dec 35

The clinical pharmacokinetics of remoxipride, a pure enantiomer, have been studied in healthy volunteers and patients. After oral administration the drug is rapidly and almost completely absorbed with a bioavailability above 90%. Thus remoxipride is a low clearance drug, with a systemic plasma clearance of about 120 ml/min, and without any first-pass metabolism. The apparent volume of distribution is 0.7 1/kg, about 80% being bound to plasma proteins (mainly alpha 1-acid glycoprotein). Remoxipride has a plasma half-life in the range of 4-7 h and is eliminated by both hepatic metabolism and renal excretion. Slightly more than 70% of the dose is recovered as urinary metabolites and about 25% is excreted unchanged. Steady-state plasma levels are reached within 2 days, and they increase linearly with doses up to 600 mg daily. There is no evidence that active metabolites of remoxipride are present in the blood. Decreased renal function is associated with increased levels of remoxipride, whereas moderate cirrhosis of the liver only slightly affects elimination. There are no pharmacokinetic interactions between remoxipride and diazepam, ethanol, biperiden, or warfarin.
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PMID:Clinical pharmacokinetics of remoxipride. 197 86

C4b-binding protein (C4bp), a glycoprotein involved in regulating the classical pathway of the complement system, binds the activated form of C4b and accelerates the decay rate of the C4b, C2a complex. Recently, sequence analysis of the cDNA for proline-rich protein (PRP) demonstrated that PRP is identical with C4bp. We measured the concentration of C4bp in serum by single radial immunodiffusion in patients with various liver diseases. Concentration of C4bp was significantly lower in hepatic cirrhosis (P = 0.001) and higher in fatty liver (P = 0.0002) than the control values, after adjusting for age, sex, and concentration of total cholesterol, triglyceride, and C-reactive protein. Significant positive correlations were observed between the concentration of C4bp in serum and total protein, albumin, cholinesterase level, and lecithin-cholesterol acyltransferase activity. Immunohistochemical analysis of human liver with specific antiserum to human C4bp demonstrated reaction endproducts in the hepatocytes around the central veins. These observations provide evidence that C4bp is synthesized by hepatocytes.
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PMID:Evidence that C4b-binding protein (proline-rich protein) is synthesized by hepatocytes. 204 87

The variability of the serum binding of the short-acting narcotic analgesic alfentanil was studied. Binding of alfentanil was measured in human alpha 1-acid glycoprotein (AAG) and human albumin solutions, and in serum from 6 groups of individuals: control subjects, patients with renal failure, cirrhosis, rheumatoid arthritis and myocardial infarction, and intensive care patients. Alfentanil is mainly bound to AAG and the influence of a change of the AAG concentration on its binding is much more marked than that of a change of the albumin concentration. In patients with renal failure, myocardial infarction and rheumatoid arthritis and in intensive care patients, AAG concentrations are increased, but alfentanil binding is significantly increased only in patients with myocardial infarction. In patients with cirrhosis, AAG, albumin concentrations, and alfentanil binding are decreased. In vitro addition of lidocaine, disopyramide, bupivacaine and quinidine, in concentrations that are observed clinically, lead only with disopyramide to an important increase in free fraction of alfentanil (from 7 to 19%). This latter finding was confirmed in 2 volunteers, treated chronically with disopyramide.
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PMID:Binding of alfentanil to human alpha 1-acid glycoprotein, albumin and serum. 207 Dec 61

The plasma protein binding of ketoconazole, an oral antifungal agent of a weak basic nature, was measured after the addition of the drug (10 micrograms.ml-1) to serum from 35 healthy individuals, ten patients with chronic renal disease and seven patients with hepatic cirrhosis. The percentage of free ketoconazole was markedly increased in patients with chronic renal disease and in patients with hepatic cirrhosis, when it was compared with the group of healthy volunteers (7.33 +/- 0.11 in renal patients; 6.12 +/- 1.43 in hepatic patients compared with 2.93 +/- 0.12 in healthy individuals). The binding ratio of ketoconazole in health and disease was significantly related to plasma albumin concentration, but not to plasma alpha 1-acid glycoprotein (AAG) concentration. Moreover, ketoconazole binds to isolated human serum albumin in a greater proportion but does not bind to isolated AAG indicating that human serum albumin is the major binding protein for this drug in plasma.
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PMID:Serum binding of ketoconazole in health and disease. 207 84

Sex hormone binding globulin (SHBG) is a glycoprotein possessing high affinity binding for 17 beta-hydroxysteriod hormones such as testosterone and oestradiol. It is probably synthesized in the liver, plasma concentrations being regulated by, amongst other things, androgen/oestrogen balance, thyroid hormones, insulin and dietary factors, it is involved in transport of sex steroids in plasma and its concentration is a major factor regulating their distribution between the protein-bound and free states. Its detailed role in the delivery of hormones to target tissues is not yet clear. Plasma SHBG concentrations are affected by a number of different diseases, high values being found in hyperthyroidism, hypogonadism, androgen insensitivity and hepatic cirrhosis in men. Low concentrations are found in myxoedema, hyperprolactinaemia and syndromes of excessive androgen activity. Concentrations are also affected by drugs such as androgens, oestrogens, thyroid hormones and anti-convulsants. Measurement of SHBG is useful in the evaluation of mild disorders of androgen metabolism and enables identification of those women with hirsutism who are more likely to respond to oestrogen therapy. Testosterone:SHBG ratios correlate well with both measured and calculated values of free testosterone and help to discriminate subjects with excessive androgen activity from normal individuals.
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PMID:Sex hormone binding globulin: origin, function and clinical significance. 208 Aug 56

Serum CA 19-9 was determined in 83 control subjects, 99 patients with pancreatic cancer, 104 with chronic pancreatitis and 137 with extra-pancreatic diseases mainly of gastrointestinal origin in order to evaluate whether hepatic factors can influence circulating CA 19-9 in pancreatic cancer. Sensitivity, specificity and accuracy of this test in determining pancreatic malignancy were: 74%, 83% and 57%. We divided patients into two groups: group A (159 cases) and group B (181 cases) with and without anatomical liver damage (presence of primary or metastatic cancer, cirrhosis, hepatitis, steatofibrosis, cholangitis). Group A presented higher CA 19-9 values as compared to group B. Significant correlations were found in group B but not in group A between CA 19-9 and ALT, ALP and total bilirubin. Multiple regression analysis (CA 19-9 dependent and ALT, ALP and total bilirubin predictor variables) was significant only in group B. The standardized partial regression coefficients found to be significant were those of ALP and total bilirubin. We can conclude that CA 19-9 is an index of pancreatic cancer with satisfactory sensitivity and specificity. The presence of anatomical liver damage seems to increase the value of this index, probably releasing CA 19-9 into the bloodstream. Extra-hepatic cholestasis may also be an important factor in elevating CA 19-9 probably by reducing the hepatic catabolism of this glycoprotein.
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PMID:How does liver dysfunction influence serum CA 19-9 in pancreatic cancer? 213 20

1. The binding of tianeptine to human plasma, isolated plasma proteins, red blood cells and to plasma from patients with cirrhosis or renal failure was studied in vitro by equilibrium dialysis. 2. Tianeptine is highly bound to plasma (95%) at therapeutic concentrations (0.3-1 microM). No saturation of the binding sites was seen. 3. Human serum albumin (HSA) was shown to be mainly responsible for this binding (94%) with a saturable process characterized by one binding site with a moderate affinity (Ka = 4.2 x 10(4) M-1) and a non-saturable process with a low total affinity (nKa = 1.2 x 10(4) M-1). 4. Like many basic and amphoteric drugs, tianeptine showed a saturable binding to alpha 1-acid glycoprotein (AAG) with one site and a moderate affinity (Ka = 3.7 x 10(4) M-1). Its binding to lipoproteins and red blood cells (RBC) was weak and non-saturable. Over the range of therapeutic drug concentrations (0.3-1 microM), the unbound fraction in blood remains constant (4.5%). 5. Interactions were studied using non-esterified fatty acids (NEFA) at pathological concentrations; they altered tianeptine binding to plasma and to isolated HSA. Tianeptine seems to bind to a HSA site different from sites I (warfarin) and II (diazepam), but close to site II. It also shares the only basic-site on AAG. However, at therapeutic drug concentrations (0.3-1 microM), not all of these interactions occur. 6. The binding of tianeptine varied according to HSA, AAG and NEFA concentrations both in patients and healthy subjects. In patients with chronic renal failure having high NEFA concentrations the unbound fraction of tianeptine (fu) increased from 0.045 to 0.153 compared with normal (P less than 0.001). In cirrhotic patients, with relatively low HSA concentrations, the fu of tianeptine increased from 0.045 to 0.088 compared with normal (P less than 0.01). 7. Multiple regression analysis of all of the data indicated that the fu of tianeptine was related significantly to HSA, NEFA and AAG concentrations, with a particularly strong correlation with NEFA concentrations. Therefore, variation of HSA and NEFA concentrations in patients on maintenance therapy may cause an increase of tianeptine fu.
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PMID:Tianeptine binding to human plasma proteins and plasma from patients with hepatic cirrhosis or renal failure. 229 64

Binding of drugs can vary considerably. Therefore, binding of the calcium antagonist diltiazem was studied in protein solutions and in serum of healthy persons, patients with renal failure, patients with cirrhosis, patients with rheumatoid arthritis, patients with myocardial infarction, and intensive care patients. The effect of in vitro addition of some cardiovascular drugs (lidocaine, disopyramide, quinidine, and bupivacaine) on the binding of diltiazem in serum of healthy volunteers was also investigated. Diltiazem is bound as well to alpha 1-acid glycoprotein (AAG) as to albumin. In patients with renal failure, myocardial infarction, and rheumatoid arthritis and in intensive care patients, AAG concentrations are increased, and in the patients with myocardial infarction an increased binding of diltiazem is found. In patients with cirrhosis, AAG concentrations and diltiazem binding are decreased. In vitro addition of lidocaine, disopyramide, bupivacaine, or quinidine in concentrations between 5 and 100 micrograms/mL, before dialysis, decreases the binding of diltiazem; the displacing effect is most pronounced with bupivacaine.
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PMID:Binding of diltiazem to albumin, alpha 1-acid glycoprotein and to serum in man. 234 78

C-reactive protein (CRP) and alpha 1-acid glycoprotein (alpha 1-GPA) two acute phase reactants, have both been monitored in patients suffering from hepatocellular diseases, compared with healthy subjects. Immunochemical findings, in hepatic amebiasis, revealed a higher incidence of increased alpha 1-GPA levels (86% of patients, as compared to 46% for CRP), whereas during liver primitive cancer and cirrhosis inverse pattern occurs. In viral chronic hepatitis, lesser perturbations were observed. In contrast, a simultaneous increase of both proteins is strong supporting evidence for the severity of disease with an unfavourable prognostic.
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PMID:[Evaluation of the inflammatory process in hepatic disorders: immunochemistry of C alpha-reactive protein and of alpha 1-acid glycoprotein]. 235 Aug 38


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