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 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

Colchicine in a dose of 200 micrograms kg body weight/day (5 days/week) was administered to groups of Schistosoma mansoni infected mice 12 weeks post infection, either alone or following previous praziquantel therapy at the 8th week of infection. Certain groups received colchicine for 6 weeks and others received it for 10 weeks. Colchicine alone did not significantly change the light microscopic appearance of schistosomal liver fibrosis, or hepatic collagen content estimated histomorphometrically, and did not reduce the elevated IL-2 serum level. Colchicine induced hepatic injury consisted of intense inflammatory reaction in granuloma and portal tracts, hepatocytic degeneration, and elevation of serum AST and ALT levels. Colchicine seemed to postpone granulomatous reaction healing and collagen deposition rather than inhibiting collagen formation or degrading it. Colchicine inhibited proliferation of hepatocytes of infected mice by expanding G2-M phases of cell cycle, thus reduced Ag NOR count and raised cell ploidy and cyclic AMP serum level. Subsidence of schistosomal infection by praziquantel prior to colchicine therapy greatly reduced inflammatory cellular reaction, significantly diminished hepatic collagen deposition and serum IL-2 level, minimized the elevated nuclear ploidy and cyclic AMP serum level that followed colchicine therapy when administered alone.
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PMID:Colchicine therapy for hepatic murine schistosomal fibrosis: image analysis and serological study. 1036 84

Circulating uremic substances are thought to be involved in the progression of chronic renal failure (CRF). An oral adsorbent AST-120 (Kremezin) is effective in removing circulating uremic toxins from the gastrointestinal tract, and retards the progression of CRF. AST-120 is widely used as an approved drug in Japan for the treatment of undialyzed uremic patients to delay the progression of CRF. AST-120 attenuates the progression of glomerular sclerosis and interstitial fibrosis in a variety of experimental rat models of CRF. However, the mechanism by which AST-120 delays the progression of CRF had not been clear. We have demonstrated that indoxyl sulfate, a dietary protein metabolite, is a circulating uremic toxin stimulating glomerular sclerosis and interstitial fibrosis, and that AST-120 decreases the serum and urine levels of indoxyl sulfate by adsorbing its precursor, indole, in the intestine. The administration of indoxyl sulfate to uremic rats stimulated the expression of transforming growth factor (TGF)-beta1, tissue inhibitor of metalloproteinase (TIMP)-1 and pro-alpha1(I)collagen in the kidneys. Further, the administration of AST-120 to uremic rats reduced the extent of glomerular sclerosis and interstitial fibrosis as well as the renal expression of TGF-beta1 and TIMP-1, by reducing the serum and urine levels of indoxyl sulfate. We propose the protein metabolite hypothesis that endogenous protein metabolites such as indoxyl sulfate play an important role in the progression of CRF, and that AST-120 is effective in retarding the progression of CRF by removing these protein metabolites through intestinal absorption.
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PMID:Preventive effects of an oral sorbent on nephropathy in rats. 1068 68

Traditional Chinese medicine is still being extensively used for treatment of liver disease in China. The anti-viral herbs, Phyllanthus amarus, P. niruri and P urninaria, and Oxymatrine extracted from Sophora flavecientis and S. subprostratae, have been shown to have a remarkable HBV suppressing effect with a serum conversion rate for HBeAg and HBV DNA around 45%, similar to that of IFN-alpha. The anti-inflammatory compound, Stronger NeoMinophagen C (SNMC), is a Japanese preparation of glycerrhizin, extracted from Glyceriza glabra, which has shown an effective rate of ALT and AST normalization and reduction to < 60 U/L in 65.6%, and 73.5% of patients. Compound 861, made of 10 herbs with Salvia miltiorrhiza as its chief component, has been shown experimentally to be effective in suppressing fibrogenesis, enhancing collagen degradation, and inhibiting TIMP expression. Clinically, an open trial of 2,000 patients showed improvement of symptoms in 83% and normalization of serum ALT in 82%. In a controlled study of 107 patients with HBV-related diseases, double liver biopsies showed that the fibrosis reversal rate after 6 months treatment with Cpd 861 was 78% in S2, 82% in S3 (precirrhotic stage) and 75% in S4 (early cirrhosis), as assessed by Scheuer's and Chevallier's criterion. In conclusion, traditional Chinese medicine has great potential in the treatment of chronic hepatitis B.
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PMID:Treatment of chronic liver diseases with traditional Chinese medicine. 1092 85

Over 90% of intravenous heroin addicts (IVHAs) carry the hepatitis C virus (HCV). The other hepatitis viruses, A, B, D, and G are relatively unimportant in IVHAs compared to HCV although active hepatitis B may demonstrate a chronic, degenerative course identical to that of HCV. The clinical course of HCV and active hepatitis B may span three or more decades. It is helpful to classify patients as in the active, cirrhosis, or liver failure stages. Only in the active, early stage are the liver enzymes, ALT and AST, likely to be elevated. It is this stage that will most likely respond to antiviral therapy. HCV has so many extra-hepatic manifestations including immune suppression, collagen diseases, and possibly lymphoma and leukemia that the disease is best termed HCV syndrome rather than simple hepatitis.
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PMID:Hepatitis C, B, D, and A: contrasting features and liver function abnormalities in heroin addicts. 1128 27

The similarities between clinical features of erythema infectiosum and collagen disease or other viral infections prompted us to investigate clinical manifestations and laboratory data of parvovirus B19 (B19) infection in adults. We diagnosed all five patients as acute B19 infection by antibody assays. The age of patients ranged from 18 to 39 years old (mean 29), and all patients were female. All five patients showed high fever, arthralgia and edema of the extremities. Four of the five patients showed skin rash of the extremities or cheeks. Two patients were diagnosed as erythema infectiosum by family physicians before coming to us. The three remaining patients were suspected to be systemic lupus erythematosus, adult Still disease or rubella indivisually and referred to our hospital. A-27-old female (case 5) visited our hospital because of polyarthralgia and butterfly rash on her face. A test for antinuclear antibodies (ANA) was positive at a dilution of 1:320. Rheumatoid factor (RF) was also detected by latex fixation test. Her AST was 51 IU/L, ALT 68 IU/L and LDH 568 IU/L. Her symptoms persisted for 3 weeks and hepatic dysfunction recovered within 3 weeks. Five months later. ANA was negative at the dilution of less than 1:40. We suggest that the similarities between some symptoms of B19 infection and clinical and serological manifestation of collagen diseases merit closer attention.
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PMID:[Five cases of erythema infectiosum in adults]. 1149 63

AIM:To investigate effect of losartan, an AT1 receptor antagonist, on hepatic fibrosis induced by CCl(4); and to determine whether or not AT1 receptors are expressed on hepatic stellate cells. METHODS AND RESULTS:Fifty male Sprague-Dawley rats, weighing (180 plus minus20)g, were randomized into five groups (control group, model group, and three losartan treated groups), in which all rats were given the subcutaneous injection of 40% CCl(4)(every 3 days for 6 weeks) except for rats of control group. Rats of losartan-treated groups were treated with losartan (20 mg/kg, 10 mg/kg, 5 mg/kg, daily gavage). After 6 weeks liver tissue and serum samples of all rats were examined. Serum hyaluronic acid (HA), procollagen type III (PC III) were detected by radioimmunoassays. van Giesion collagen staining was used to evaluate the extracellular matrix of rats with liver fibrosis. The expression of AT1 receptors, transforming growth factor-beta (TGF-beta), and alpha-smooth muscle actinalpha-SMA) in liver tissue were determined by immunohistochemical techniques. Compared with model group, serum ALT and AST of losartan-treated groups were significantly reduced (italic>t = 4.20,P < 0.01 and italic>t = 4.57,P < 0.01). Serum HA and PC III also had significant differences (italic>t = 3.53,P<0.01 and t=2.20, P<0.05). The degree of fibrosis was improved by losartan and correlated with the expressions of AT1 receptors, TGF-beta, and alpha-SMA in liver tissue.CONCLUSION:AT1 receptor antagonist, losartan, could limit the progression of the hepatic fibrosis induced by CCl(4). The mechanism may be related to the decrease in the expression of AT1 receptors and TGF-beta, ameliorating the injury of hepatocytes; activation of local renin-angiotensin system might relate to hepatic fibrosis; and during progression of fibrosis, activated hepatic stellate cells might express AT1 receptors.
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PMID:Effects of AT1 receptor antagonist, losartan, on rat hepatic fibrosis induced by CCl(4). 1181 43

We previously reported that zeaxanthin dipalmitate (ZD), a carotenoid from Lycium chinense fruit, reduces myofibroblast-like cell proliferation and collagen synthesis in vitro. To determine whether ZD might reduce the severity of hepatic fibrosis in an animal model, hepatic fibrosis was induced in rats by bile duct ligation/scission (BDL) for a period of 6 weeks. Treatment of BDL rats with ZD at a dose of 25 mg/kg body weight significantly reduced the activities of aspartate transaminase (p<0.05) and alkaline phosphatase (p<0.001) in serum. Furthermore, collagen deposition was significantly reduced as assessed by the Sirius Red binding assay in BDL rats administered ZD at the dose of 25 mg/kg body weight (p<0.01). In addition, the levels of thiobarbituric acid-reactive substances and 4-hydroxyproline were reduced when BDL rats received ZD at the dose of 25 mg/kg body weight. These results showed that ZD effectively inhibited hepatic fibrosis in BDL rats, at least in part via its antioxidative activity.
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PMID:Zeaxanthin dipalmitate from Lycium chinense fruit reduces experimentally induced hepatic fibrosis in rats. 1191 41

Liver fibrosis is a prepathological state wherein damaged liver tissues in chronic liver diseases, such as hepatitis, are not repaired to normal tissues, but converted to fibrous tissue. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a cancer chemopreventive agent, is effective against a wide variety of chemical carcinogens. Recently, we reported that oltipraz inhibits liver fibrogenesis (Kang et al., 2002). In the present study, the effects of oltipraz in combination with dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB) on dimethylnitrosamine (DMN)-induced liver fibrogenesis were assessed in rats. Oltipraz (30 mg/kg body weight, p.o., 3 times per week for 4 weeks) was found to inhibit the increases in plasma ALT, AST and bilirubin by DMN, whereas DDB (30 mg/kg body weight, p.o., 3 times per week for 4 weeks) attenuated the increases in the plasma ALT and bilirubin. The lowered plasma protein and albumin contents in DMN-treated rats were completely restored by oltipraz, but not by DDB. DDB decreases liver cell injury and inflammation through inhibition of nuclear factor-kB. DMN increased the accumulation of liver collagen, as indicated by the increase in the 4-hydroxyproline content in liver homogenates, which was reduced by treatment with oltipraz, but not by DDB. Given the differential effect between oltipraz and DDB, the potential enhancement of antifibrotic efficacy by the drugs was assessed in the animal model. Despite the minimal effect of DDB on DMN-induced fibrogenesis, DDB (5-25 mg/kg), administered together with oltipraz (25-5 mg/kg), showed an additive protective effect against hepatotoxicity and fibrosis induced by DMN, which was shown by the blood chemistry parameters and histopathological analysis. The adequate composition ratio of oltipraz to DDB was 5:1. These results provide information on the pharmaceutical composition, comprising of oltipraz and DDB as the active components, for the treatment and/or prevention of liver fibrosis and cirrhosis.
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PMID:The anti-fibrogenic effect of a pharmaceutical composition of [5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione] (oltipraz) and dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB). 1243 1

We investigated the incidence of recurrence after resection of small hepatocellular carcinomas (HCC) in patients infected with hepatitis C virus (HCV) to determine the appropriate surgical management of these patients. Sixty-one patients with anti-HCV antibody who underwent curative liver resection for small HCC (<or= 2.0 cm in greatest diameter) were categorized into two groups. Group 1 consisted of 27 patients with serum concentrations of type IV collagen 7S domain (7S collagen), a marker for hepatic fibrosis, < 8 ng/ml. Group 2 consisted of 34 patients with serum concentrations of 7S collagen >or= 8 ng/ml. Serum concentration of 7S collagen correlated with the severity of active hepatitis and the degree of fibrosis in the noncancerous hepatic tissue, both of which are related to risk potential of hepatocarcinogenesis. Serum concentration of total bilirubin, aspartate aminotransferase activity, indocyanine green retention rate at 15 minutes, the proportion of patients who were Child-Pugh class B, and the proportion of patients with severe active hepatitis or cirrhosis (determined by histologic examination) were significantly higher in group 2 than in group 1. Platelet count was significantly lower in group 2. Tumor-free survival rates were not different between the groups. In group 1, nonanatomic resection was a risk factor for recurrence by univariate and multivariate analyses (odds ratio = 3.45, p = 0.040). In group 2, nonanatomic resection was not a risk factor for recurrence. In patients with small HCV-related HCC, anatomic resection is recommended when the serum concentration of 7S collagen is low (< 8 ng/ml) because the potential of hepatocarcinogenesis may be low even after the operation.
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PMID:Appropriate surgical management of small hepatocellular carcinomas in patients infected with hepatitis C virus. 1265 89


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