Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective was to evaluate the rationale for liver needle biopsy versus blood liver functional tests in monitoring the incidence of hepatotoxicity in Egyptian rheumatoid arthritic patients treated with gold compounds. Forty patients (12 males, 28 females) were randomly selected out of 258 Egyptian rheumatoid arthritic patients treated with sodium auro-thiomalate during the past 4 years. The minimum duration of treatment was 40 weeks. The methods used were firstly, liver function tests (serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, total serum bilirubin and total serum albumin) before, weekly during and after administration of sodium auro-thiomalate. Secondly, a needle liver biopsy was conducted by using the tru-cut needle. Then liver histology was graded according to Roenigk for grading liver toxicity. Viral hepatitis markers (hepatitis B surface antigen, anti-hepatitis C virus were done for monitoring viral hepatitis. Finally, the liver tissue contents of heavy metals were counted in the cases that showed grade IIIB histological changes. The results showed that none of the studied cases developed any clinically significant liver disease during the course of chrysotherapy. Blood liver function tests were of normal value throughout the course of drug administration. According to Roenigk grading, 20 patients (50%) showed grade I liver changes, and the other 20 patients showed liver changes of grades II and III (four grade II, eight grade IIIA, and another eight grade IIIB). None of the patients showed grade IV liver changes. It was concluded that blood liver tests are not the most sensitive methods to detect hepatotoxicity in gold-receiving Egyptian rheumatoid arthritic patients. Needle liver biopsy is not superior in detecting liver toxicity, compared with routine laboratory liver function tests, because of its complications. Rheumatoid arthritic patients with a potential risk of clinically significant liver disease should not be exposed to the risk of gold salt therapy. Pretreatment HLA-DR genetic typing may be a good detector for rheumatoid arthritic patients with potential risk of hepatotoxicity.
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PMID:Liver toxicity profile in gold-treated Egyptian rheumatoid arthritis patients. 960 32

The purpose of this study was to relate dose-dependent hepatotoxicity stemming from prolonged exposure to sublethal concentrations of the cyclic heptapeptide microcystin-LR (Mcyst) to hepatic Mcyst concentrations and protein phosphatase activity. Mcyst is a potent inhibitor of protein phosphatase types 1 and 2A (PP1 and PP2A). Twenty male Sprague-Dawley rats were infused continuously with 0, 3, 6, or 9 micrograms Mcyst/day for 28 days using intraperitoneal mini-osmotic pumps containing highly purified toxin or saline. At the end of 28 days, dose-dependent increases in several serum biochemical tests including sorbitol dehydrogenase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and bile acids had occurred. Serum albumin decreased in a dose-dependent fashion. Liver activity of both PP1 and PP2A decreased in a dose-dependent manner, but with a relatively greater effect on PP2A than PP1. Liver cytosol Mcyst concentrations, measured by direct competitive ELISA, also increased in a dose-dependent manner, although at a higher rate than would be predicted from the incremental increase in dose given. This disproportional increase is suggestive of the bioaccumulation of Mcyst with increasing dose. Histopathological abnormalities included hepatocellular apoptosis and cytosolic vacuolation of principally zone 3 hepatocytes. Immunohistochemical stains revealed Mcyst predominantly within pericanalicular regions of zone 3 hepatocytes. It was concluded that prolonged exposure to sublethal concentrations of Mcyst results in multiple dose-dependent hepatotoxic effects that correspond to decreased hepatic serine/threonine protein phosphatase activity and increasing cytosolic Mcyst concentrations. The disproportional increase of hepatic Mcyst concentrations observed may suggest the bioaccumulation of toxin and an increasing relative risk of hepatotoxicity with increasing dose.
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PMID:Prolonged sublethal exposure to the protein phosphatase inhibitor microcystin-LR results in multiple dose-dependent hepatotoxic effects. 972 Jan 45

The mechanisms by which alcohol intake, particularly moderate alcohol intake, effects bone metabolism are poorly defined. We have examined the relationship between mineral metabolism and recent self-reported alcohol intake (SRAI) across a wide range of such intakes in a series of 104 men aged 32 to 78 years of age in an outpatient setting. A morning nonfasting urine, serum specimen and recent SRAI were obtained from each subject. SRAI was reported as between 0 and 45 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin (r = 0.30, p = 0.002), alkaline phosphatase (r = 0.30, p = 0.004), and aspartate aminotransferase (SGOT) (r = 0.29, p = 0.006). SRAI correlated with serum calcium corrected for albumin (r = -0.39, p < 0.001), estradiol (r = 0.43, p < 0.001), and immunoreactive parathyroid hormone (iPTH) (r = -0.51, p < 0.001), as well as urinary calcium (per 100 mg of creatinine) (r = 0.55, p < 0.001). We have arbitrarily divided the participants into two groups on the basis of their reported alcohol intake. Individuals in the first group had intakes ranging from none to moderate intake (drank 8.4 oz or less of ethanol per week, equivalent to an average of two drinks daily or less). Those in the second group had moderate or heavier intake, with >8.4 oz of ethanol intake/week. Mean serum iPTH was significantly greater in those in the first group (none to moderate), compared with the second group (moderate or heavier) (56.0 +/- 3.4 and 39.9 +/- 2.0 pM/liter, respectively). Calcium corrected for serum albumin was significantly greater in individuals in the first, compared with the second, group (9.23 +/- 0.05 vs. 8.88 +/- 0.07 mg/dl, respectively). In addition, urinary calcium (corrected per 100 mg of creatinine) was significantly lower in the former, compared with the latter (3.1 +/- 0.4 vs. 8.4 +/- 1.1 mg/100 mg of creatinine, respectively). Similarly, urinary excretion of collagen crosslinks (corrected per 100 mg of creatinine) was significantly less in men in the second group, compared with the first group (316 +/- 38 vs. 530 +/- 78 nM/100 mg of creatinine, respectively). Not surprisingly, a series of correlations between iPTH and age, 250-hydroxyvitamin D, and testosterone were significant in individuals with none to moderate SRAI, but not moderate or heavier SRAI. Significant independent predictors of serum iPTH in the entire group of men were age (beta = 0.215, p = 0.025), SRAI (beta = -0.281, p = 0.003), 250-hydroxyvitamin D (beta = -0.309, p = 0.002), and testosterone (beta = -184, p = 0.048). We have concluded that, in free-living men, alcohol intake >8.4 oz/week was associated with decreased serum iPTH concentrations.
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PMID:Effect of recent alcohol intake on parathyroid hormone and mineral metabolism in men. 975 55

The aim of this study was to assess the influence of human immunodeficiency virus (HIV) infection on chronic hepatitis B. In a series of 132 (65 anti-HIV positive) homosexual non-drug addicted men with chronic hepatitis B, the liver function was assessed with biochemical tests; the degree of hepatitis B virus (HBV) replication was assessed with serum HBV DNA level and with immunoperoxidase staining of hepatitis B core (HBc) antigen on liver specimens; and the severity of liver lesions was assessed with an histology activity index. Anti-HIV-positive and anti-HIV-negative patients were not different for serum aspartate transaminase activity, bilirubin, prothrombin, and histology activity index. Anti-HIV-positive patients had lower serum alanine transaminase activity levels (P =.0001), lower serum albumin levels (P =.0009), and higher serum HBV DNA levels (P =.01). There was a higher prevalence of cirrhosis in anti-HIV-positive patients (P =.04). In homosexual men with chronic hepatitis B, HIV infection is associated with a higher level of HBV replication and a higher risk for cirrhosis without increased liver necrotico-inflammatory process.
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PMID:Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men. 1077 55

Severe alcoholic liver injury has been relatively rare, but is gradually increasing in Japan. The clinical features and prognostic factors in severe alcoholic liver injury were retrospectively investigated in 105 patients, consisting of 3 with severe alcoholic hepatitis (SAH), 43 with cirrhosis with superimposed alcoholic hepatitis [liver cirrhosis (LC)+alcoholic hepatitis (AH)], 38 with AH, and 21 with alcoholic cirrhosis. Seven of the 105 patients (6.7%, 2 with SAH and 5 with LC+AH) died of hepatic failure. Patients with SAH showed severe hyperbilirubinemia, reduced hepatic biosynthetic capacity, and marked acute inflammatory reactions, and developed multiple organ failure, such as disseminated intravascular coagulation (DIC), renal failure, acute pancreatitis, or pneumonia. Two SAH patients died within 1 month, whereas five with LC+AH died within 77 days during the second episode of AH. In these nonsurvivors, the serum total bilirubin (T.Bil) level was not normalized, and the hepaplastin test (HPT), serum albumin, cholesterol, and platelet count were not markedly improved after the first episode of AH. In the survivors, elevation of AST lasted longer, and the improvement of T.Bil, hepatic biosynthetic capacity, and the platelet count were much less in patients with LC+AH than in those with AH. Multivariate analysis using the Cox proportional hazards model showed serum C-reactive protein (CRP) and DIC as significant independent prognostic factors among SAH, LC+AH, and AH groups. When factors related to multiple organ failure, such as DIC and renal failure, were excluded, T.Bil and CRP were selected as independent prognostic factors. In patients with LC+AH and AH, CRP, and HPT were shown to be significant independent prognostic factors. These results suggest that SAH with multiple organ failure, and another episode of AH in advanced LC with hyperbilirubinemia and reduced hepatic biosynthetic capacity, are indicative of an extremely poor prognosis in chronic alcoholics.
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PMID:Prognostic factors in severe alcoholic liver injury. Nara Liver Study Group. 1023 76

Patients with homozygous (PiZ) alpha(1)-antitrypsin (AAT) deficiency have not only low baseline serum AAT levels (approximately 10 to 15% normal) but also an attenuated acute phase response. They are susceptible to the development of premature emphysema but may also be particularly susceptible to lung damage during bacterial exacerbations when there will be a significant neutrophil influx. The purposes of the present study were to assess the inflammatory nature of acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) in subjects with AAT deficiency, to compare this with COPD patients without deficiency, and to monitor the inflammatory process and its resolution following appropriate antibacterial therapy. At the start of the exacerbation, patients with AAT deficiency had lower sputum AAT (p < 0.001) and secretory leukoprotease inhibitor (SLPI; p = 0.02) with higher elastase activity (p = 0.02) compared with COPD patients without deficiency. Both groups had a comparable acute phase response as assessed by C-reactive protein (CRP) but the AAT-deficient patients had a minimal rise in serum AAT (to < 6 microM). After treatment with antibiotics, in patients with AAT deficiency, there were significant changes in many sputum proteins including a rise in SLPI levels, and a reduction in myeloperoxidase (MPO) and elastase activity (p < 0. 005 for all measures); the sputum chemoattractants interleukin-8 (IL-8) and leukotriene B(4) (LTB(4)) fell (p < 0.01), and protein leak (sputum/serum albumin ratio) became lower (p < 0.01). The changes were rapid and within 3 d of the commencement of antibiotic therapy the biochemical markers had decreased significantly, but took a variable time thereafter to return to baseline values. In conclusion, patients with AAT deficiency had evidence of increased elastase activity at the start of the exacerbation when compared with nondeficient COPD patients which probably reflects a deficient antiproteinase screen (lower sputum AAT and SLPI). The increased bronchial inflammation at presentation resolved rapidly with 14 d of antibiotic therapy.
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PMID:Evidence for excessive bronchial inflammation during an acute exacerbation of chronic obstructive pulmonary disease in patients with alpha(1)-antitrypsin deficiency (PiZ). 1058 15

To determine the decision level of liver function in the most elderly patients, we compared serum albumin, aspartate aminotransferase(AST), alanine aminotransferase(ALT) and alkaline phosphatase(ALP) values of the most elderly patients > 85 years with those of healthy young adults. Two hundred fifty five elderly people, aged 88-106 years and average 96.6 years(171 women, 84 men), were included in this study. Elderly people were divided into four groups according to their activities of daily living(ADL), 114 Rank-J: free living, 62 Rank-A: unable to go outside without help, 39 Rank-B: bedridden but able to sit up in bed and 40 Rank-C: completely bedridden. Serum albumin values for the most elderly patients in Rank-J were 4.2 +/- 0.3 g/dl for women and 4.0 +/- 0.3 g/dl for men, showing marked decrease from those of young healthy adults aged 19-59 years(p < 0.0001). In 22.2% of elderly women and 44.2% of elderly men, albumin values deviated from the reference interval of young adults. ALT value for the most elderly patients also showed a decrease in both sexes and AST and ALP values for the most elderly patients showed an increase in women compared with young adults. However, these were minor deviations from the reference interval for young adults. In ADL-stratified groups of the most elderly patients, serum albumin values showed marked decrease with decline in ADL, whereas AST, ALT and ALP values remained constant in both sexes regardless of ADL.
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PMID:[Liver function of the most elderly patients]. 1080 30

We describe two females, 15 and 23 years old, respectively, who presented with classical features of Wilson's disease (WD) and several features of autoimmune hepatitis (AIH). The first patient was initially diagnosed as AIH and treated with prednisolone which caused clinical improvement, with an increase of serum albumin from 22 to 30 g/L, and a decrease of aspartate aminotransferase from 103 to 47 U/L. Subsequent diagnosis of WD and introduction of penicillamine gave excellent improvement and complete normalization of liver function tests. The second patient, at first also diagnosed as having AIH, was treated with steroids and azathioprine with initial improvement, but subsequent deterioration. The diagnosis of WD was made 2 years after initial diagnosis of AIH, as the patient reached end-stage liver disease and required a transplant. Therefore, d-penicillamine treatment was not attempted. We conclude that, in patients with AIH, a thorough screening for WD is necessary, particularly when the response to steroid therapy is poor. Conversely, in patients suffering from WD with superimposed features of AIH, a combination of steroids and penicillamine may be of benefit.
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PMID:Wilson's disease with superimposed autoimmune features: report of two cases and review. 1467 55

The participation of cytokines in the early stage mechanism of hepatocyte proliferation has already attracted attention. We investigated the effect of methylprednisolone (MDS), which inhibits the inflammatory response, given before and after a 70% partial hepatectomy in rats on the kinetics of tumor necrosis factor-alpha and Interleukin-6, liver cell function and the rate of liver regeneration. Serum Interleukin-6 levels of the MDS groups were significantly lower than those of the control group. Serum alanine aminotransferase, aspartate aminotransferase and hyaluronic acid levels were also significantly decreased, however, the serum albumin level showed high values in the MDS groups. In the MDS groups, MIB-5 labeling indices, a novel antibody reactive with the equivalent Ki-67 protein, which detects immunohistochemically all active parts of the cell cycle in the rat liver, were more pronounced than in the control group at an earlier time. However, in regard to 5-bromo-2-deoxyuridine (BrdU), there were no significant differences among the three groups. There were no differences in residual liver weight/body weight between the three groups after 336 h. In our study, MDS administration before or after a 70% partial hepatectomy decreased serum Interleukin-6 levels, and inhibited hepatic dysfunction. Therefore, we considered that beneficial effects of physiological doses of MDS in the peri-operative period should be confirmed in humans.
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PMID:Effect of methylprednisolone on the kinetics of cytokines and liver function of regenerating liver in rats. 1113 81

Although there have been many studies of the risk factors for recurrence after resection of hepatocellular carcinoma (HCC), the subjects were patients with various viral status in the previous studies, and hepatitis C viremia has not been evaluated. We investigated risk factors, including hepatic C viremia and histologic findings of noncancerous hepatic tissue, for recurrence after resection of hepatitis C virus (HCV)-related HCC. A total of 223 patients who underwent liver resection for HCV-related HCC were studied. HCV viremia, laboratory data, degree of HCC malignancy, histologic findings in noncancerous hepatic tissue, preoperative interferon therapy, and operative methods were evaluated for recurrence risk by univariate and multivariate analyses. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin, and the proportion of patients with a high histologic activity score (mild to severe active hepatitis) were significantly higher in patients with HCV viremia than in those without viremia. Serum albumin was significantly lower in patients with HCV viremia. By univariate analysis, older age (> 65 years old), HCV viremia, elevated AST (> 40 IU/L) and ALT (> 45 IU/L), large tumors (> 40 mm), multiple HCCs, moderately or poorly differentiated HCC, portal invasion, mild to severe active hepatitis, and lack of preoperative interferon therapy were risk factors for recurrence. Multivariate analysis showed that older age, HCV viremia, high AST, multiple HCCs, and portal invasion were independent risk factors. For HCV-related HCCs, not only the degree of malignancy of the HCC but also HCV viremia and active hepatitis are risk factors for recurrence.
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PMID:Risk factors for recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. 1119 23


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