Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Labeling of platelets in vivo by 75Se -- Selenomethionine (75Se-M) was performed in nine cases of hepatic cirrhosis and thrombocytopenia for evaluation of the kinetics of platelet maturation. Folic acid and vitamin B12 deficiency was excluded by pretreatment of the patients with these agents. The platelet maturation time -- time between the injection of the isotope and maximum radioactivity of separated blood platelets -- was shortened to 7.7 +/- 1.1 days (mean +/- SD) compared to the normal 9.1 +/- 1.4 days. For explanation a disturbance of megakaryocyte maturation and/or platelet release from the bone marrow is suggested.
 ...
PMID:In vivo labeling of platelets with 75Se -- selenomethionine in patients with hepatic cirrhosis and thrombocytopenia. 57 16

To make liver biopsy unnecessary in certain cases, PGA (P, prothrombin time; G, gamma-glutamyl transpeptidase; A, apoliprotein AI), a simple biological index combining a specific test for severe liver disease (prothrombin time), a sensitive test of alcoholic liver disease (serum gamma-glutamyl transpeptidase), and a test for liver fibrosis (serum apolipoprotein AI), was evaluated in a training sample of 333 drinkers and validated in 291 other drinkers. All patients underwent an intercostal liver biopsy, and the specimen was independently read by two pathologists. The PGA index varied from 0 to 12. When PGA was less than or equal to 2, the probability of cirrhosis was 0% and the probability of normal liver or minimal changes 83%. Conversely, when PGA was greater than or equal to 9, the probability of normal liver or minimal changes was 0% and the probability of cirrhosis 86%. These values did not vary between training and validation periods, between asymptomatic vs. symptomatic subjects or between PGA at admission vs. PGA 1 week later. This index could be useful for general practitioners in identifying subjects at high risk for severe alcoholic liver disease.
 ...
PMID:A simple biological index for detection of alcoholic liver disease in drinkers. 179 91

Methotrexate has been associated with chronic toxicities such as cirrhosis and neurological impairments ranging from mild learning disorders to a fatal leucoencephalopathy. The mechanism(s) for this toxicity is not completely understood. Certain tissues can convert methotrexate to polyglutamates. This results in a more persistent intracellular form of the drug. In this study the intracellular levels of folate and methotrexate were measured in the erythrocytes and liver of patients treated chronically with methotrexate. These tissues showed an accumulation of methotrexate as polyglutamates and a concomitant loss of folate. Folate concentrations were below normal in nine of 12 red cell and three of five liver samples. It is proposed that persistent methotrexate concentrations and/or the associated folate deficiency may be related to the toxicity of methotrexate, especially in time of cellular stress.
 ...
PMID:Methotrexate accumulation and folate depletion in cells as a possible mechanism of chronic toxicity to the drug. 617 Mar 7

Alpha-2-macroglobulin (A2M) is a proteinase inhibitor. Cells synthesizing A2M are in first-order hepatocytes and in second-order activated Ito cells (in culture starting at day 4-5 after seeding). This study was undertaken in 525 alcoholic patients with different histological stages of alcoholic liver disease to assess if the A2M could improve the diagnostic value of PGA index for detection of cirrhosis or fibrosis among drinkers, particularly in patients without clinical symptoms of liver failure and portal hypertension, and to assess the specific correlation of serum A2M with the score of liver fibrosis adjusted for steatosis and alcoholic hepatitis and thereafter adjusted for GGT, PT, and ApoA1, the three components of the PGA index. In 525 alcoholic patients, we have demonstrated the independent diagnostic value of A2M. The predictive values of the weighted score, using linear discriminant function combining PT, GGT, ApoA1 and A2M of the PGAA score and of the PGA score were assessed in a training step and validated in a second step. Then, 316 alcoholic clinically asymptomatic patients were studied. In these patients, the discriminant function permitted correct classification of 72% of patients. The PGAA index had comparable diagnostic value with 70% of patients correctly classified. On the other hand, the PGA index including only PT, GGT, and ApoA1 had classified correctly less patients (65%) than the discriminant function and the PGAA index (P < 0.01). For a value of 7, PGAA had 79% specificity and 89% sensitivity for the diagnosis of cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Alpha-2-macroglobulin and hepatic fibrosis. Diagnostic interest. 752 68

In early hepatic fibrosis, increased amounts of type III collagen are deposited. Persistently high serum concentrations of aminoterminal type III procollagen propeptide (PIIIP) correlate with the activity of the fibrogenic process. Another index for the detection of fibrosis, the PGA index, combines the prothrombin time, gamma-glutamyl transpeptidase activity, and serum apolipoprotein A1 concentration (the latter falls with progressive fibrosis). We compared PIIIP measurements and PGA index in patients with various histological forms of alcoholic liver disease (104), primary biliary cirrhosis (38), and chronic B virus hepatitis (27), and in healthy age-matched controls (30). The ability of each test to identify correctly patients with fibrosis or cirrhosis was assessed with receiver operating curves. The PGA index was much higher in all groups of patients with alcoholic liver disease than in controls (p < 0.0001). PIIIP concentrations were also substantially higher than in controls (p < 0.05 for fatty liver, p < 0.0001 for all other groups), especially in the group with alcoholic hepatitis and cirrhosis. For the detection of cirrhosis the PGA was 91% sensitive and 81% specific and the PIIIP concentration was 94% sensitive and 81% specific. The two tests combined had 85% sensitivity, but 93% specificity. Among patients with primary biliary cirrhosis, both PGA index and PIIIP concentration correlated well with the severity of the disease, determined by the Mayo score (r = 0.72 and 0.66 respectively). The combined tests were 96% sensitive for the detection of fibrosis. All patients with chronic B virus hepatitis had raised PGA and PIIIP values in comparison with controls (p < 0.0001) but there were no differences between subgroups. Substantially raised PIIIP concentrations thus identify the subgroup of alcoholic patients with both hepatitis and cirrhosis. The combination of PGA index and PIIIP concentration may be useful for targeting treatment with antifibrotic drugs and to reduce the need for liver biopsy.
 ...
PMID:Comparison of serum procollagen III peptide concentrations and PGA index for assessment of hepatic fibrosis. 790 68

Previously, we have found that intracellular calcium homeostasis is altered in platelets from an experimental model of liver cirrhosis, the bile-duct ligated (BDL) rat; these alterations are compatible with the existence of a hypercoagulable state. Different studies indicate that cholestatic diseases are associated with hyperhomocysteinemia; thus, we hypothetized that it could contribute to those platelet alterations. In the present study, we have investigated the role of homocysteine (HCY) in platelet aggregation and calcium signaling in the BDL model. The effect of chronic folic acid treatment was also analyzed. Acute treatment with HCY increased the aggregation response to ADP and calcium responses to thrombin in platelets of control and BDL rats. Capacitative calcium entry was not altered by HCY. Chronic treatment with folic acid decreased platelet aggregation in control and BDL rats, but this decrease was greater in BDL rats. In folic acid-treated rats, thrombin-induced calcium entry and release were decreased in platelet of control rats but unaltered in BDL rats; however, capacitative calcium entry was decreased in platelets of control and BDL rats treated with folic acid. Reactive oxygen species were produced at higher levels by BDL platelets after stimulation with HCY or thrombin and folic acid normalized these responses. HCY plays a role in the enhanced platelet aggregation response of BDL rats, probably through an enhanced formation of ROS. Folic acid pretreatment normalizes many of the platelet alterations shown by BDL rats.
 ...
PMID:Role of homocysteine and folic acid on the altered calcium homeostasis of platelets from rats with biliary cirrhosis. 2815 May 25