Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum creatine kinase (CK) activity is reduced in some conditions, including rheumatic diseases, but the aetiology and significance remain to be clarified. The aim of this study was to investigate relationships between serum CK activity and other muscle enzymes, muscle mass, renal function, steroid use and disease activity in patients with rheumatic diseases. Serum CK activity was measured in sera from 498 patients with rheumatic diseases: rheumatoid arthritis (RA, n = 145), systemic lupus erythematosus (SLE, n = 31), spondyloarthropathies (SpA, n = 35), polyarthralgia/arthritis (Poly, n = 74), miscellaneous group (MI, n = 46), and in non-inflammatory arthropathies (NIA, n = 167) as controls. Serum CK level was significantly reduced in RA (45.4 +/- 1.9 IU/l), SLE (46.4 +/- 4.2 IU/l), SpA (64.7 +/- 5.6 IU/l) and MI (63.4 +/- 4.8 IU/l), but not in poly (70.2 +/- 3.1 IU/l), compared to controls (78.9 +/- 2.4 IU/l) (P < 0.05). CK values correlated with aspartate aminotransferase (AST), erythrocyte sedimentation rate (ESR), body mass index (BMI) and platelets (Plat) in RA; ESR and haemoglobin (Hb) in SLE, AST, ESR and Hb in SpA; lactate dehydrogenase (LDH), AST, ESR and Hb in Poly; LDH, AST, ESR, Hb and Ccr in MI; and LDH, AST and ESR in controls. In all patients with rheumatic diseases CK level was significantly correlated with LDH, AST, alanine aminotransferase (ALT), ESR, C-reactive protein (CRP) and BMI and prednisolone dose, but not with Ccr, age and disease duration. In conclusion, our data support the possibility that reduced CK activity is inversely correlated with inflammatory activity and correlated with other muscle enzymes, muscle mass and steroid use, but not with renal function, age and disease duration in rheumatic diseases.
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PMID:Serum creatine kinase in patients with rheumatic diseases. 1094 12

To clarify the role of IP-10 in autoimmune liver diseases, we studied the serum levels of IP-10 in 14 patients with autoimmune hepatitis (AIH), 23 patients with primary biliary cirrhosis (PBC), and 65 patients with chronic viral hepatitis (20 type B and 45 type C). The hepatic expression of IP-10 mRNA and the correlation between the serum levels of IP-10 and clinical parameters were also evaluated. In addition to 20 healthy controls, 16 rheumatoid arthritis (RA) patients were included as an extrahepatic inflammatory disease. The serum level of IP-10 was significantly (P < 0.02) higher in patients with AIH, PBC, and chronic hepatitis B and C than in healthy controls, and it was significantly correlated (P < 0.05) with the serum levels of aspartate aminotransferase and alanine aminotransferase in patients with AIH, PBC, and chronic hepatitis B and C. The serum level of IP-10 was not elevated in RA patients. After successful treatment of AIH and chronic hepatitis C, the serum level of IP-10 decreased to the same level as in healthy volunteers. As we previously showed in cases with chronic hepatitis B or C, in situ hybridization in both AIH and PBC cases demonstrated the expression of IP-10 mRNA in hepatocytes around focal or lobular necrosis surrounded by infiltrating mononuclear cells, whereas IP-10 mRNA was not expressed in areas around the damaged bile ducts in PBC cases. The present results suggest that IP-10 is specifically produced by hepatocytes in inflammatory areas irrespective of the aetiology of hepatitis, and that IP-10 may help to recruit T cells to the hepatic lesions in autoimmune liver diseases as well as in chronic viral hepatitis.
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PMID:Increase of chemokine interferon-inducible protein-10 (IP-10) in the serum of patients with autoimmune liver diseases and increase of its mRNA expression in hepatocytes. 1120 58

Many patients with rheumatoid arthritis (RA) have low plasma pyridoxal-phosphate (PLP) but a normal erythrocyte aspartate aminotransferase activity coefficient (alpha EAST), a measure of vitamin B-6 status in the erythrocytes, compared with healthy subjects. The goal of the present study was to examine the correlations of PLP levels in these two compartments (plasma and erythrocytes) with other established indices of vitamin B-6 status, and to determine which indicator better reflects functional status of vitamin B-6 in patients with RA. Multiple indices of vitamin B-6 status were measured in 33 patients with RA. Plasma PLP, urinary 4-pyridoxic acid (4-PA), net increase in plasma total homocysteine after a methionine load (DeltatHcy) and net increase in urinary xanthurenic acid after a tryptophan load (DeltaXA) were log-transformed to reach normality for statistical analyses. We found that log-plasma PLP levels were inversely correlated with both log-DeltatHcy (r = -0.368, P = 0.035) and log-DeltaXA (r = -0.333, P = 0.05). Plasma PLP was not correlated with alpha EAST or urinary 4-PA excretion. In contrast, erythrocyte PLP was inversely correlated with alpha EAST (r = -0.431, P = 0.012) and positively correlated with log-4-PA (r = 0.475, P = 0.005), but erythrocyte PLP was not correlated with the outcomes of a methionine or tryptophan load test. Erythrocyte PLP and log-4-PA, but not plasma PLP, were correlated with dietary intake of vitamin B-6 after adjusting for protein intake (r = 0.420, P = 0.015 and r = 0.333, P = 0.05, respectively). We suggest that in patients with RA, plasma PLP levels are a better diagnostic indicator of functional vitamin B-6 status than erythrocyte PLP levels.
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PMID:Plasma pyridoxal 5'-phosphate concentration is correlated with functional vitamin B-6 indices in patients with rheumatoid arthritis and marginal vitamin B-6 status. 1267 18

Previously we observed strong and consistent associations between vitamin B6 status and several indicators of inflammation in patients with rheumatoid arthritis. Clinical indicators, including the disability score, the length of morning stiffness, and the degree of pain, and biochemical markers, including the erythrocyte sedimentation rate and C-reactive protein levels, were found to be inversely correlated with circulating vitamin B6 levels. Such strong associations imply that impaired vitamin B6 status in these patients results from inflammation. In the present study we examined whether inflammation directly alters vitamin B6 tissue contents and its excretion in vivo. A cross-sectional case-controlled human clinical trial was performed in parallel with experiments in an animal model of inflammation. Plasma and erythrocyte and pyridoxal 5'-phosphate concentrations, urinary 4-pyridoxic acid excretion, and the activity coefficient of erythrocyte aspartate aminotransferase were compared between patients and healthy subjects. Adjuvant arthritis was induced in rats for investigating hepatic and muscle contents as well as the urinary excretion of vitamin B6 during acute and chronic inflammation. Patients with rheumatoid arthritis had low plasma pyridoxal 5'-phosphate compared with healthy control subjects, but normal erythrocyte pyridoxal 5'-phosphate and urinary 4-pyridoxic acid excretion. Adjuvant arthritis in rats did not affect 4-pyridoxic acid excretion or muscle storage of pyridoxal 5'-phosphate, but it resulted in significantly lower pyridoxal 5'-phosphate levels in circulation and in liver during inflammation. Inflammation induced a tissue-specific depletion of vitamin B6. The low plasma pyridoxal 5'-phosphate levels seen in inflammation are unlikely to be due to insufficient intake or excessive vitamin B6 excretion. Possible causes of decreased levels of vitamin B6 are discussed.
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PMID:Inflammation causes tissue-specific depletion of vitamin B6. 1627 78

Patients with rheumatoid arthritis have subnormal vitamin B6 status, both quantitatively and functionally. Abnormal vitamin B6 status in rheumatoid arthritis has been associated with spontaneous tumor necrosis factor (TNF)-alpha production and markers of inflammation, including C-reactive protein and erythrocyte sedimentation rate. Impaired vitamin B6 status could be a result of inflammation, and these patients may have higher demand for vitamin B6. The aim of this study was to determine if daily supplementation with 50 mg of pyridoxine for 30 days can correct the static and/or the functional abnormalities of vitamin B6 status seen in patients with rheumatoid arthritis, and further investigate if pyridoxine supplementation has any effects on the pro-inflammatory cytokine TNF-alpha or IL-6 production of arthritis. This was a double-blinded, placebo-controlled study involving patients with rheumatoid arthritis with plasma pyridoxal 5'-phosphate below the 25th percentile of the Framingham Heart Cohort Study. Vitamin B6 status was assessed via plasma and erythrocyte pyridoxal 5'-phosphate concentrations, the erythrocyte aspartate aminotransferase activity coefficient (alphaEAST), net homocysteine increase in response to a methionine load test (DeltatHcy), and 24 h urinary xanthurenic acid (XA) excretion in response to a tryptophan load test. Urinary 4-pyridoxic acid (4-PA) was measured to examine the impact of pyridoxine treatment on vitamin B6 excretion in these patients. Pro-inflammatory cytokine (TNF-alpha and IL-6) production, C-reactive protein levels and the erythrocyte sedimentation rate before and after supplementation were also examined. Pyridoxine supplementation significantly improved plasma and erythrocyte pyridoxal 5'-phosphate concentrations, erythrocyte alphaEAST, urinary 4-PA, and XA excretion. These improvements were apparent regardless of baseline B6 levels. Pyridoxine supplementation also showed a trend (p < 0.09) towards a reduction in post-methionine load DeltatHcy. Supplementation did not affect pro-inflammatory cytokine production. Although pyridoxine supplementation did not suppress pro-inflammatory cytokine production in patients with rheumatoid arthritis, the suboptimal vitamin B6 status seen in rheumatoid arthritis can be corrected by 50 mg pyridoxine supplementation for 30 days. Data from the present study suggest that patients with rheumatoid arthritis may have higher requirements for vitamin B6 than those in a normal healthy population.
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PMID:Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve inflammation in patients with rheumatoid arthritis. 1627 93

Alcoholic liver disease and hepatitis C are associated with the production of autoantibodies such as rheumatoid factors (RF), which bind to IgG and can aid in host defence, but are also associated with pathological conditions such as rheumatoid arthritis. Because little is known about the role of RF in liver disease, we characterized the RF production that either occurred spontaneously in response to alcohol consumption or was induced by injection of an Escherichia coli glycolipoprotein in C57Bl/6 mice. Whereas severe liver damage was induced by carbon tetrachloride (CCl(4)), minimal damage was caused by chronic alcohol consumption. Liver damage was monitored by measurements of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Circulating RF was induced in response to chronic alcohol consumption; the latter probably involved Toll-like receptor ligation. In contrast, CCl(4)-induced damage was not associated with RF induction. However, concurrent treatment with an E. coli glycolipoprotein macromolecule that induced RF, protected against CCL(4)-induced liver damage as measured by a highly significant decrease (P = 0.008) at 4 weeks in AST and ALT. RF induced by E. coli glycolipoprotein correlated with 'protection' from liver damage, indicating that the RF autoimmune response does not necessarily exacerbate liver disease.
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PMID:Rheumatoid factor induction in murine models of liver injury. 1722 74

A 50-year-old woman was admitted for active rheumatoid arthritis (RA). She was found to have RA 1 year prior to this admission. Past history was unremarkable and she had no family history for rheumatic diseases. As nonsteroidal anti-inflammatory drug (NSAID) and methotrexate were not effective, etanercept was started (25 mg, twice a week). Mild elevation of alanine transaminase (ALT) and aspartate transaminase (AST) was found as an outpatient, and it was considered to be NSAID-induced liver injury. Two weeks after the first dose of etanercept, she developed progressive elevation of AST and ALT with right upper quadrant tenderness and hepatomegaly. Etanercept was discontinued and liver biopsy was performed, which demonstrated portal-area-dominant lymphoplasmacytic inflammatory cell infiltration. She was diagnosed as autoimmune hepatitis (AIH). Glucocorticoid was started with normalized liver function and stable joint symptoms. AIH was thought to be acutely aggravated by the administration of etanercept.
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PMID:A case of autoimmune hepatitis exacerbated by the administration of etanercept in the patient with rheumatoid arthritis. 1879 97

At present, there is no consensus regarding the utility of liver enzyme monitoring in rheumatology patients undergoing treatment with azathioprine (AZA). To further investigate this issue, we retrospectively reviewed for current or past use of AZA all patient records in our Disease Modifying Antirheumatic Drug (DMARD) clinic from May 1986 through September 1996. Information available from individual DMARD charts included AZA data (dates initiated, dose, indication for changing dose or stopping AZA), co-administered DMARDs, and aspartate aminotransferase (AST) serum values. In patients followed in the clinic through February 1994, serum alkaline phosphatase (AP) values additionally were available. Published reports of AZA hepatotoxicity in rheumatoid arthritis (RA) patients were found by a MEDLINE search, supplemented by a manual search of reference lists.We screened 429 patient records, and all patients who had received AZA at any time during the study period (n = 56) were identified for further review. The mean daily AZA dose was 96 mg (median = 100 mg/ day, range = 25-200 mg/day). All of the 56 patients had undergone routine periodic monitoring of serum AST while taking AZA (mean interval = 26 days); 30 of these patients additionally underwent monitoring of serum AP (mean interval = 24 days). Twenty-three (41%) of the patients had at least one episode of an abnormally elevated serum AST and/or AP while taking AZA. Only 1 of these 2 laboratory values was abnormal in 12 patients. The average time from AZA initiation to first appearance of an abnormal AST and/or AP value was 27 days (range = 7-62 days). During observation alone, all abnormal laboratory test results became normalized in 20 of 23 patients (87%) during the study period. There were no interventions in response to an abnormal laboratory value, and no patient experienced an adverse clinical outcome attributable to AZA hepatotoxicity during the 10-year study period.AZA use for rheumatic conditions may be associated with elevations in both the serum AST and/or AP values. Most of these elevations were transient, and none were clinically significant in our patient population. This study supports current American College of Rheumatology guidelines, which do not recommend routine periodic monitoring with liver enzyme tests in RA patients taking AZA. Furthermore, this study suggests that the utility of the baseline liver enzyme test in these patients is not well established.
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PMID:Azathioprine hepatotoxicity is uncommon in patients with Rheumatic diseases. 1907 58

An understanding of the cytokine cascade in a rheumatoid joint has led to the development of new therapeutic options, including drugs targeting tumor necrosis factor-alpha (TNF-alpha). The safety profile of these agents in patients with hepatitis-induced liver disease, however, remains a concern because of risks associated with immune suppression. To examine the effect of three different TNF-alpha antagonists, infliximab, etanercept, and adalimumab, on serum transaminases and hepatitis viral load in patients with rheumatoid arthritis (RA) and concurrent hepatitis B (HBV) or hepatitis C (HCV). Medical records of 11 patients with diagnosis of RA and documented seropositivity for hepatitis B or hepatitis C were retrospectively reviewed for worsening of hepatic inflammation and viral proliferation as measured by a rise in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and viral load while using these agents. Three patients had RA with concurrent chronic HBV and eight patients had RA with concurrent chronic HCV. Seven patients remained on a single anti-TNF-alpha agent and four patients switched to a second anti-TNF-alpha agent due to treatment failure. Two patients showed a transient elevation in AST and/or ALT from normal, but in all 11 patients, AST and ALT levels were within one time the upper range of normal at the conclusion of the study. No significant increase in viral load was seen except one patient who showed a fourfold increase from baseline. Our case series supports results obtained from previous studies examining the safety of anti-TNF-alpha agents in patients with underlying hepatic disease. Use of these agents in patients with HBV or HCV may be associated with a transient transaminitis but appears to be safe overall. In both groups, frequent monitoring of serum transaminase levels and viral load is essential.
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PMID:Use of tumor necrosis factor-alpha (TNF-alpha) antagonists infliximab, etanercept, and adalimumab in patients with concurrent rheumatoid arthritis and hepatitis B or hepatitis C: a retrospective record review of 11 patients. 1929 50

In this report, we describe a case of a 48-year-old Japanese woman who is a hepatitis B (HB) carrier with rheumatoid arthritis (RA). She had the following antibody profile: HBs Ag(+), HBs Ab(-), HBe Ag(-), HBe Ab (+), HBc Ab(-) and undetectable HBV-DNA level. She was treated with auranofin, salazosulfapyridine, and bucillamine. Finally, she was treated with D: -penicillamine, but her disease activity remained elevated. Prophylactic treatment of entecavir 0.5 mg daily was started in March 2008 and all disease-modifying anti-rheumatic drugs were stopped. After 2 weeks, etanercept monotherapy was started at 25 mg subcutaneously once a week. Significant improvement in clinical parameters of disease activity and well being was observed. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and HB virus viral load did not change significantly. Serum ALT, AST, and HB virus viral load were followed-up at every 3-month intervals, from initiation of therapy up to 24 months after the start of treatment with etanercept. We have also summarized the course of nine RA patients who received etanercept and were HB carriers or had chronic HB according to our literature search. Based on the results of our study, treatment of these patients with etanercept co-administered with lamivudine or entecavir appears to be safe.
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PMID:Effect of etanercept and entecavil in a patient with rheumatoid arthritis who is a hepatitis B carrier: a review of the literature. 2006 98


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