Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several beneficial effects of splenectomy on the liver integrity have been recently reported by both experimental and clinical studies. However, the effects of splenectomy on hepatic functional reserve and structural damage in patients with chronic hepatitis C (CHC) were not studied by objective evidence. The aim of this study was to assess the effect of splenectomy on hepatic functional reserve and structural damage in patients with CHC by non-invasive serum markers. The study involved 22 patients with histopathological diagnosis of CHC undergoing splenectomy for treatment of associated hypersplenism. The hepatic functional reserve and structural damage markers were assessed before and after splenectomy surgery on the 2nd and 60th postoperative days by aspartate aminotransferase to alanine aminotransferase (AST/ALT ratio), AST to platelet ratio index (APRI) and serum levels of gamma-glutamyl transferase (GGT), hyaluronic acid (HA), type IV collagen (CIV) and tissue inhibitor of metalloproteinase-1 (TIMP-1). After splenectomy, the levels of serum HA showed a significant decrease in relation to the preoperative values both in PO-1 (mean pre-splenectomy: 272+/-88.6 versus 185+/-77.4 ng/ml; P=0.01) and PO-2 (169+/-58.1 ng/ml; 0.017). The levels of type IV collagen showed a significant decrease in relation to the preoperative values both in PO-1 (mean pre-splenectomy: 208+/-134 versus 125+/-100 ng/ml; P=0.01) and PO-2 (121+/-74.7 ng/ml; P=0.02). Serum levels of TIMP-1 also showed a significant decrease in relation to the preoperative values both in PO-1 (mean pre-splenectomy: 764+/-571 versus 261+/-195 ng/ml; P=0.006) and PO-2 (149+/-110.1 ng/ml; P=0.004). There was no significant difference between PO-1 and PO-2 mean values for each of those serum markers. This study found that splenectomy induced a reduction of biochemical markers of liver functional reserve and fibrosis in patients with chronic hepatitis C which reflect a change in the processes involved in of liver fibrosis. However, it cannot be concluded whether this reflects a change in the rate of its progression or a prevention of further fibrosis.
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PMID:A study of the effect of splenectomy on hepatic functional reserve and structural damage in patients with chronic hepatitis C virus infection by non-invasive serum markers. A prospective study. 1866 98

Bidens bipinnata L. is well known in China as a traditional Chinese medicine and has been used to treat hepatitis in clinics for many years. In a previous study we found that total flavonoids of Bidens bipinnata L. (TFB) had a protective effect against carbon tetrachloride (CCl4)-induced acute liver injury in mice. Now this study was designed to investigate its therapeutic effect against CCl4-induced liver fibrosis in rats and to determine, in part, its mechanism of action. The liver fibrosis model was established by subcutaneous injection of 50% CCl4 twice a week for 18 weeks. TFB (40, 80 and 160 mg kg(-1)) was administered by gastrogavage daily from the 9th week. The results showed that TFB (80 and 160 mg kg(-1)) treatment for 10 weeks significantly reduced the elevated liver index (liver weight/body weight) and spleen index (spleen weight/body weight), elevated levels of serum transaminases (alanine aminotransferase and aspartate aminotransferase), hyaluronic acid, type III procollagen and hepatic hydroxyproline. In addition, TFB markedly inhibited CCl4-induced lipid peroxidation and enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. Moreover, TFB (80 and 160 mg kg(-1)) treatment improved the morphologic changes of hepatic fibrosis induced by CCl4 and suppressed nuclear factor (NF)-kappaB, alpha-smooth muscle actin (SMA) protein expression and transforming growth factor (TGF)-beta1 gene expression in the liver of liver fibrosis of rats. In conclusion, TFB was able to ameliorate liver injury and protect rats from CCl4-induced liver fibrosis by suppressing oxidative stress. This process may be related to inhibiting the induction of NF-kappaB on hepatic stellate cell activation and the expression of TGF-beta1.
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PMID:Protective effects of total flavonoids of Bidens bipinnata L. against carbon tetrachloride-induced liver fibrosis in rats. 1881 33

Chronic hepatitis C virus (HCV) infection follows an accelerated course in patients co-infected with human immunodeficiency virus (HIV); establishing the extent of liver fibrosis is crucial for disease staging and determining treatment strategy in these patients. The utility of noninvasive markers of fibrosis as alternatives to liver biopsy has not been well-studied in these patients. We evaluated the predictive value of serum transforming growth factor-beta1 (TGF-beta1) and hyaluronic acid (HA) levels for determining the extent of liver fibrosis. Liver biopsies and blood samples were collected from 69 consecutive patients (74% male; median age, 41 years) between May 2005 and November 2006. Serum TGF-beta1 and HA were analysed using commercial kits. Aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase levels were elevated in 81%, 70% and 60% of patients, respectively. Fifty-three patients (90%) were on highly active antiretroviral therapy and the median CD4-positive cell count was 422 cells/microL. The extent of fibrosis according to Scheuer's scoring was 32% F0 (no fibrosis), 16.5% F1, 16.5% F2, 26% F3 and 7% F4 (cirrhosis). Mean serum TGF-beta1 was 36.1 +/- 14.4 ng/mL; mean serum HA was 75.2 +/- 85.0 microg/L. Serum HA was positively associated and significantly correlated with the stage of fibrosis (r = 0.56; P < 0.05). The area under the curve for discriminating mild (F0-F2) from significant (F3-F4) fibrosis in receiver operating analysis using HA was 0.83 (sensitivity, 87%; specificity, 70%). These data suggest that HA is clinically useful for predicting liver fibrosis and cirrhosis in patients co-infected with HCV/HIV. However, serum TGF-beta1 was not predictive of histological damage in co-infected individuals treated with HAART.
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PMID:Hyaluronic acid, transforming growth factor-beta1 and hepatic fibrosis in patients with chronic hepatitis C virus and human immunodeficiency virus co-infection. 1920 Jan 32

Noninvasive liver fibrosis scores are evaluated in hepatitis C virus-infected patients but are less known in liver transplant recipients. Fibrosis is a frequent, multifactorial event in these patients. This preliminary retrospective study reviewed the diagnostic performance of 3 simple scores for liver fibrosis in transplant patients: namely, APRI (aspartate aminotransferase to platelet ratio index), FORNS (platelets, gamma-glutamyltransferase, patient age, and cholesterol), and FIB-4 (patient age, aspartate aminotransferase, alanine aminotransferase, and platelets). Ninety-four biopsies were collected from 50 liver transplant recipients at a mean period after orthotopic liver transplantation (OLT) of 30.7 months (range, 12-108 months). The indications for OLT were hepatitis C in 23% of cases, hepatitis B in 14%, alcoholic disease in 33%, cholestatic disease in 19%, and others in 11%. According to the Metavir classification, 72% of biopsies revealed no significant histological fibrosis (F0-1 = group 1) and 28% showed significant fibrosis (F2-4 = group 2). A correlation was observed between the histological stage of fibrosis and albumin, gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, and hyaluronic acid levels. APRI and FIB-4 correlated significantly with the histological stage of fibrosis both globally and in the subgroup of nonhepatitis C liver recipients. When APRI and FIB-4 tests were applied to predict fibrosis (area under the receiver operating characteristic curve), the results were 0.87 and 0.78, respectively. Values were not significant with the FORNS test. In conclusion, APRI and FIB-4 enabled accurate prediction of significant fibrosis after OLT. In the nonhepatitis C subgroup, we found similar predictive performances. These simple scores may be applied in clinical practice in the context of follow-up after OLT independent of hepatitis C status.
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PMID:APRI and FIB-4 Scores Are Useful After Liver Transplantation Independently of Etiology. 1932 55

A series of methylenedioxybenzene compounds were synthesized and found to have hepatoprotective effects in chemical-induced hepatotoxicity models. The purpose of the present study was to investigate the anti-fibrotic effects of a synthetic methylenedioxybenzene compound, CW209292, using the dimethylnitrosamine (DMN)-induced chronic liver injury model in rats. Liver injuries were induced in Sprague Dawley rats by injection of DMN (intraperitoneally, 10 microl/kg) 3 times per week for 4 weeks. The rats were treated with CW209292 (per os, 25 or 75 mg/kg/d) for 4 weeks. Treatment of rats with DMN for 4 weeks resulted in significant decreases in serum albumin levels, whereas concomitant treatment with CW209292 prevented these decreases. CW209292 treatment also shortened prothrombin time prolonged by DMN, providing evidence that the agent was active in preserving liver function against DMN insult. DMN treatment caused marked increases in plasma bilirubin, aspartate aminotransferase (AST), alanine transaminase (ALT), and hyaluronic acid levels; CW209292 treatment reversed these increases. CW209292 also significantly reduced hepatic hydroxyproline content as well as hepatic fibrosis and inflammation in histological examination. Additionally, immunochemically detectable hepatic collagen type IV and alpha-smooth muscle actin levels were decreased by CW209292 treatment. Proliferation of hepatic stellate cells isolated from DMN-treated rats was inhibited by CW209292. Furthermore, tumor growth factor (TGF)-beta1 mRNA expression was increased in DMN-treated rats, whereas CW209292 treatment prevented these increases. These results suggest that CW209292 exhibits anti-fibrotic effects in Sprague Dawley rats with DMN-induced hepatic fibrosis by blocking the mRNA expression of TGF-beta1 and subsequent inhibition of the proliferation of hepatic stellate cells.
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PMID:Anti-fibrotic effects of a methylenedioxybenzene compound, CW209292 on dimethylnitrosamine-induced hepatic fibrosis in rats. 1965 75

The effect of sevoflurane anesthesia with or without induced hypotension on hepatocellular integrity was studied. Forty adult consented patients scheduled for various urological procedures were allocated randomly to either NTG group (nitroglycerin-induced hypotension) or a control group of twenty patients each. Anesthesia was induced and maintained by fentanyl, sevoflurane & vecuronium in both groups. In NTG group, nitro-glycerin infusion was adjusted to maintain mean arterial pressure (MAP) of 50-65 mm Hg. Specific and sensitive hepatic biomarkers; alpha (alpha) and pi (pi) glutathione S-transferases (GST) and hyaluronic acid (HA), also traditional liver enzymes; aspartate (AST) and alanine (ALT) aminotransferases were measured at: TO (pre-induction), T1, T2, T3 (15, 30 & 60 minutes after MAP stabilization respectively) and T4 (24 hours after anesthesia end). Plasma alpha-GST significantly increased at T3 in control group (p < 0.05) and in NTG group (p < 0.01) compared to TO in same group. In NTG group, hyaluronic acid con-centrations was significantly increased at T1, T2 (p < 0.05) and T3 (p < 0.01) from T0. Compared to control group, alpha- GST & HA concentrations showed significant increases in NTG group at T3 with p < 0.05 then returned back to normal range at T4. But, pi-GST, AST and ALT showed no significant changes throughout the study in both groups.
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PMID:Hepatocellular integrity during sevoflurane anesthesia with induced hypotension. 1979 71

Ischemia-reperfusion and chronic injuries associated with small-for-size liver transplantation (SFSLT) impair the regeneration of liver graft and induce liver fibrosis. Mesenchymal stem cells (MSCs) can prevent the development of liver fibrosis, and hepatocyte growth factor (HGF) can also attenuate liver cirrhosis. Our previous studies have demonstrated that higher occurrence of liver fibrosis existed in rats post-SFSLT, and that implantation of HGF/MSCs, the human HGF (hHGF)-expressing MSCs, can improve liver regeneration, reduce mortality of rats, as well as have the potent antifibrotic effect in this SFSLT model. In the present study, we implanted HGF/MSCs into liver grafts via the portal vein and investigated their role in antifibrosis effect, using a 30% SFSLT rat model. Fibrosis indexes, including laminin (LN), hyaluronic acid (HA) levels in serum and hydroxyproline (Hyp) content in the liver grafts, the expression of transforming growth factor-beta1 (TGF-beta(1)), rat HGF (rHGF), alpha-smooth muscle actin (alpha-SMA) in hepatic stellate cells (HSCs), alanine aminotransferase (ALT), total bilirubin (BIL), and albumin (ALB) levels in serum, in rats in different treatment groups were assessed at different time points. We found that HGF/MSCs significantly inhibited the formation of liver fibrosis in rats undergoing SFSLT, while MSCs and HGF had synergistic effects in the process. The antifibrosis effect of HGF/MSCs may have contributed in modulating the activation and apoptosis of HSCs, elevating the rHGF expression level, and decreasing the TGF-beta(1) secretion of activated HSCs. These studies suggest that HGF/MSCs may be a novel therapeutic option for the treatment of liver fibrosis after SFSLT.
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PMID:Antifibrotic effect of hepatocyte growth factor-expressing mesenchymal stem cells in small-for-size liver transplant rats. 2002 19

Baicalein was a major bioactive flavonoid derived from Radix Scutellariae in Xiao-Chai-Hu-Tang which was commonly used to treat chronic hepatitis and liver fibrosis in China. The aim of this study was to assess whether chronic baicalein administration could prevent liver fibrosis induced by carbon tetrachloride (CCl(4)) in rats and investigate its possible protective mechanism. The antifibrotic effects of baicalein were assessed directly by hepatic histology and indirectly by measuring levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), hepatic hyaluronic acid, laminin and procollagen type III (PCIII) in serum, as well as hydroxyproline and matrix metalloproteinases (MMPs) in liver. In addition, we further investigated protein synthesis of platelet derived growth factor (PDGF) beta receptor which has been identified as attractive target for therapeutic intervention. CCl(4) treatment increased levels of AST, ALT, hyaluronic acid, laminin, and PCIII in serum, as well as hydroxyproline and MMPs in liver. Baicalein treatment (20, 40, or 80 mg/kg for 10 weeks) dose-dependently decreased levels of these markers. Baicalein also reduced inflammation, destruction of liver architecture, and collagen accumulation and significantly inhibited protein synthesis of PDGF-beta receptor. Together, our results suggest that chronic baicalein administration inhibits stellate cell activation and proliferation by the down-regulation of PDGF-beta receptor and prevents the development of CCl(4) induced liver fibrosis in rats.
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PMID:Antifibrotic effects of chronic baicalein administration in a CCl4 liver fibrosis model in rats. 2007 50

We reported previously that vascular endothelial growth factor (VEGF) was increased in acetaminophen (APAP) toxicity in mice and treatment with a VEGF receptor inhibitor reduced hepatocyte regeneration. The effect of human recombinant VEGF (hrVEGF) on APAP toxicity in the mouse was examined. In early toxicity studies, B6C3F1 mice received hrVEGF (50 microg s.c.) or vehicle 30 min before receiving APAP (200 mg/kg i.p.) and were sacrificed at 2, 4, and 8 h. Toxicity was comparable at 2 and 4 h, but reduced in the APAP/hrVEGF mice at 8 h (p < 0.05) compared with the APAP/vehicle mice. Hepatic glutathione (GSH) and APAP protein adduct levels were comparable between the two groups of mice, with the exception that GSH was higher at 8 h in the hrVEGF-treated mice. Subsequently, mice received two doses (before and 10 h) or three doses (before and 10 and 24 h) of hrVEGF; alanine aminotransferase values and necrosis were reduced at 24 and 36 h, respectively, in the APAP/hrVEGF mice (p < 0.05) compared with the APAP/vehicle mice. Proliferating cell nuclear antigen expression was enhanced, and interleukin-6 expression was reduced in the mice that received hrVEGF (p < 0.05) compared with the APAP/vehicle mice. In addition, treatment with hrVEGF lowered plasma hyaluronic acid levels and neutrophil counts at 36 h. Cumulatively, the data show that treatment with hrVEGF reduced toxicity and increased hepatocyte regeneration in APAP toxicity in the mouse. Attenuation of sinusoidal cell endothelial dysfunction and changes in neutrophil dynamics may be operant mechanisms in the hepatoprotection mediated by hrVEGF in APAP toxicity.
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PMID:Human recombinant vascular endothelial growth factor reduces necrosis and enhances hepatocyte regeneration in a mouse model of acetaminophen toxicity. 2036 54

The aim of this prospective study was to investigate the diagnostic value of ultrasound elastography for evaluating liver stiffness measurement (LSM) in 74 patients with hepatitis B virus (HBV) infection, treated with telbivudine (22 with chronic HBV infection, 32 with compensated cirrhosis and 20 with decompensated cirrhosis). Each patient underwent ultrasound elastography measurements and serum liver marker assays before and after 6 months' treatment with 600 mg telbivudine, orally, once daily. In the 22 patients with chronic HBV infection, LSM values measured by ultrasound elastography decreased significantly following the treatment period compared with baseline. The LSM values were significantly higher in the 20 patients with decompensated cirrhosis than in the 32 patients with compensated cirrhosis after treatment. Significant decreases in serum hepatic fibrosis indices occurred in all patients following treatment. The correlation between fibrosis index, hyaluronic acid level and LSM was statistically significant in all patients, whereas the correlation between alanine aminotransferase and LSM was not. The findings suggest that liver stiffness in patients with HBV can be measured simply with ultrasound elastography and that it is reduced within 6 months by treatment with telbivudine. The main adverse events noted during the study period were that creatine kinase levels were increased in seven patients and that seven patients had influenza-like symptoms.
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PMID:The diagnostic value of ultrasound elastography in patients with hepatitis B virus infection: a prospective study. 2122 17


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