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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatty liver and kidney syndrome (FLKS), a naturally occurring but experimentally reproducible disease in chickens, has several clinical, pathological, and biochemical features in common with Reye's syndrome. Because of this, it has been suggested that FLKS may serve as an animal model of Reye's syndrome. We have examined, therefore, various parameters characteristic of Reye's syndrome in chickens affected with FLKS to further delineate the similarities and differences between the two disorders. Plasma glucose concentrations were significantly lower in chickens affected with FLKS which may be caused by the significantly reduced activity of pyruvate carboxylase in all FLKS-affected animals. The activity of propionyl CoA carboxylase was low in only the most severely affected chickens, and beta-methylcrotonyl CoA carboxylase showed no difference when compared with controls. This may be due to variable sensitivities of the three carboxylases to marginal biotin deficiency which occurs with FLKS. Plasma ammonia concentrations and activities of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, however, were not elevated in the affected birds. Histological changes in the liver and kidney were noted in affected chickens, but these changes were not identical with those observed in Reye's syndrome. Although the mechanisms of nitrogen elimination in fowl differ from those in humans, failure to demonstrate hyperammonemia, elevated serum transaminase activities, or similar histological changes in tissues of affected birds indicates that FLKS is not an appropriate model for the study of Reye's syndrome.
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PMID:Fatty liver and kidney syndrome in chickens as an animal model for Reye's syndrome. 664 49

Liver lipid peroxidation, nonheme iron, antioxidants, and protein oxidation were investigated in experimental alcohol-induced liver disease in the rat. Wistar male rats were intragastrically and continuously infused for 4 weeks with a high-fat diet plus an ethanol or an isocaloric amount of dextrose, maintaining a high blood alcohol level (200-300 mg%). This model induced fatty liver, spotty necrosis, and focal inflammation. This pathology was associated with an enhanced lipid peroxidation and a decrease in the major antioxidant factors. Hepatic alpha-tocopherol and glutathione concentrations were significantly decreased in ethanol-fed rats. Glutathione peroxidase (GPx) was also decreased, whereas glutathione S-transferase (GST) was unaffected. The nonheme iron level was significantly decreased. Protein oxidation was assessed through three parameters: protein thiols, protein carbonyl groups, and the activity of glutamine synthetase (GS), a centrilobular enzyme particularly susceptible to free-radical-mediated damage. Ethanol-fed rats had decreased protein thiol concentrations and reduced GS activity, together with increased protein carbonyls. A significant correlation between GS activity and the pathological score was observed. This study confirms the ethanol-related increase in lipid peroxidation and shows that ethanol impairs the hepatic antioxidant potential. Furthermore, evidence of oxidative protein damage is given, including decreased activity of a key enzyme of ammonia metabolism. These protein disturbances may contribute to the pathogenesis of the observed liver damage.
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PMID:Effect of chronic ethanol feeding on lipid peroxidation and protein oxidation in relation to liver pathology. 902 46

In forty-five Holstein Frisian dairy cows (1-6 weeks post partum; mean age: 5.1 +/- 1.2 years) the serum total bile acid concentrations (SBA) were measured enzymatically. In all cows a left sided abomasal displacement was corrected surgically by right side laparotomy and omentopexy three days before investigation. The liver fat content was determined in all cows histologically. Liver failure was assumed if typical clinical signs (ataxia, general depression, recumbency or coma), an increased venous plasma ammonia level (> 35 mumol/l) and a decreased plasma amino acid index (< 4.0) were found. Cows without liver failure (N = 29) were grouped according to the liver fat content as cows with mild (N = 5), moderate (N = 19) or severe hepatosteatosis (N = 5). Histological examination of liver biopsies in cows with liver failure (N = 16) revealed in twelve cases a severe fatty liver and in four cases a hydropic degeneration of the liver tissue. Although in cows without liver failure mean SBA concentrations were higher in the group with moderate (47.3 +/- 30.9 mumol/l) or severe fatty liver (32.9 +/- 21.7 mumol/l) than in that with mild lipidosis (18.0 (16.8 mumol/l), differences were not significant. The mean SBA concentration in cows with liver failure (70.5 +/- 49.5 mumol/l) was only significantly (p < 0.05) increased compared to cows with uncomplicated mild hepatic lipidosis. In conclusion, the determination of SBA concentrations is of little value in the recognition of fatty liver or even liver failure due to the considerable variance of SBA concentrations in dairy cows.
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PMID:Total serum bile acid concentrations in dairy cows with fatty liver and liver failure. 1002 57

Two experiments were conducted to test the following two hypotheses: 1) fatty liver could hamper hepatic conversion of ammonia to urea and increase circulating ammonia or Gln% [Gln% = Gln x 100/(Gln + Glu)] in cows around parturition; 2) decreased ureagenesis might cause alkalosis and in turn reduce blood Ca. In the first experiment, 14 Holstein cows were monitored from 27 d prepartum to 35 d postpartum. There was a rise in circulating ammonia and Gln% at calving, suggesting an increase in ammonia passing to and through the liver. Stepwise regression analysis revealed the following relationship for plasma samples at 22 h and liver triglyceride at 2 d postpartum: ammonia (microM) = 32.1+/-0.89 triglyceride (% DM), Gln% = 71.2 + 0.23 triglyceride (% DM) + 1.31 urea (mM). The positive correlation between liver triglyceride and plasma ammonia and Gln% suggests that hepatic triglyceride accumulation might inhibit ureagenesis, thereby increasing ammonia concentration at the perivenous hepatocytes where Gln synthesis occurs and increasing ammonia concentration in blood leaving the liver. In the second experiment, 28 rats were used to determine whether hepatic triglyceride accumulation, induced by choline deficiency, affects urinary ammonia N and blood pH homeostasis. There was a trend for a positive correlation between urinary ammonia N and liver triglyceride. No correlation between liver triglyceride and blood pH, bicarbonate, pCO2 or plasma Ca was found. In conclusion, hepatic triglyceride accumulation may inhibit ureagenesis and result in increased circulating ammonia, Gln% and urinary ammonia N in vivo. Hepatic triglyceride accumulation did not affect blood pH homeostasis.
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PMID:Plasma concentration of urea, ammonia, glutamine around calving, and the relation of hepatic triglyceride, to plasma ammonia removal and blood acid-base balance. 1079 89

Acute liver disease was diagnosed in three pregnant patients: two 30-year-old women had a 'haemolysis, elevated liver enzymes, low platelets' (HELLP) syndrome and acute fatty liver of pregnancy, respectively, and a 20-year-old woman had acute liver failure due to acute hepatitis B. The first two patients had a caesarean section, the third one delivered her child, which died spontaneously shortly after birth at a gestational age of 23 weeks. She was then treated by liver transplantation. All three patients left the hospital in good condition. Liver diseases in pregnancy may be pregnancy-related, e.g. the HELLP syndrome and acute fatty liver of pregnancy, but they may also be coincidental phenomena, e.g. viral hepatitis. The HELLP syndrome is often associated with pre-eclampsia, and presents with epigastric pain and thrombocytopenia with haemolysis. Acute fatty liver disease and acute liver failure due to hepatitis present with liver insufficiency characterised by anorexia, nausea, coagulopathy, hypoglycaemia and elevated serum ammonia levels. Management depends on the diagnosis and the gestational age; pregnancy complicated by acute fatty liver disease should be terminated while pregnancy complicated by the HELLP syndrome early in pregnancy may be maintained to improve the outcome of the foetus. In acute liver failure due to viral hepatitis, termination of pregnancy alone does not affect the disease.
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PMID:[The pregnant patient with acute liver disease]. 1253 8

Juvenile visceral steatosis (JVS) mouse is an animal model of human primary carnitine deficiency caused by a mutation of the gene encoding carnitine transporter, and suffers from various symptoms, such as fatty liver, growth retardation, hyperammonemia, hypoglycemia, and cardiac hypertrophy. We have shown that hyperammonemia during the weaning period (15-26 days of age) is caused by suppression of urea cycle enzyme gene expression. The suppression resulted from activation of a transcription factor, AP-1. We have found that a cis-element for AP-1 binding is present in the enhancer region of the carbamoylphosphate synthetase (CPS) gene, and that the AP-1 binding site is involved in the suppression of CPS induction by dexamethasone in cultured hepatocytes and in the suppression of CPS expression in the liver of JVS mice. The blood ammonia levels in JVS mice increased during the weaning period, and then decreased to almost control levels after 30 days of age. In this paper, we report that in adult JVS mice, ammonia levels again increased after starvation for at least 24 hr and this effect was suppressed by carnitine treatment. Starvation for 48 hr did not significantly suppress CPS activity in the liver and did not cause any change in hepatic ornithine concentration. The concentration of N-acetylglutamate in the liver of starved JVS mice was not significantly different from that of JVS mice treated with carnitine. These results indicate that the hyperammonemia in carnitine-deficient adult JVS mice during starvation and the suppression by carnitine treatment differ from those found during the weaning period, and thus the cause of hyperammonemia and the mechanism of suppression remain to be solved.
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PMID:Hyperammonemia in carnitine-deficient adult JVS mice used by starvation. 1260 12

BACKGROUND:: Nonalcoholic steatohepatitis is most often attributed to the effects of obesity, hyperlipidemia, diabetes mellitus and drugs. It is still unknown whether livers with steatohepatitis are more vulnerable to toxic damage. AIM:: To determine the effect of the hepatotoxicant thioacetamide in a rat nutritional model of hepatic steatohepatitis. METHODS:: Steatohepatitis was induced in rats by placing them on a methionine-choline deficient diet for 1 month. Thioacetamide was administered by three consecutive intraperitoneal injections (300mg/kg) at 24h intervals. RESULTS:: Following treatment with thioacetamide, the elevated serum levels of liver enzymes and blood ammonia, liver necroinflammation and the survival rate after 48h were not different between rats with normal or fatty liver. However, those parameters were significantly worse when steatohepatitis regressed after return to normal diet for 1 month (P < 0.01). Western blot analysis of hepatic extracts revealed no difference in cytochrome P4502E1 levels between livers with steatohepatitis and steatohepatitis after regression, suggesting that the enhanced hepatotoxicity after regression of steatohepatitis could not be attributed to increased cytochrome P4502E1. CONCLUSIONS:: In a nutritional model of steatohepatitis, rats with fatty liver were not more vulnerable than normal rats to liver damage induced by thioacetamide. However, liver damage was significantly more severe in rats with steatohepatitis after 1 month regression.
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PMID:Thioacetamide-induced hepatic damage in a rat nutritional model of steatohepatitis. 1558 79

Liver fatty acid binding protein has recently been shown to possess antioxidant properties but its role in liver disease, such as cholestasis, is not known. Since oxidative stress has been recognized as an important contributing factor in liver disease, we investigated the expression and antioxidative function of this protein using the bile-duct ligated model of cholestasis. Rats were divided into 3 groups: sham, bile-duct ligated and bile-duct ligated plus clofibrate. Animals were sacrificed at various time points after bile-duct ligation. RT-PCR and Western blot were used to analyze liver fatty acid binding protein expression. Cellular lipid peroxidation products were assessed by measuring thiobarbituric acid-reactive substances. Liver function was evaluated by measuring serum total bilirubin, alanine aminotransferase and ammonia. Liver fatty acid binding protein mRNA and protein levels were reduced to 51% and 20% of sham, respectively at 2 weeks following bile-duct ligation (p<0.05). The decreased liver fatty acid binding protein was associated with a statistical increase in hepatic lipid peroxidation products (224%) and decrease in hepatic function. Clofibrate treatment restored protein level and improved hepatic function. Clofibrate treatment also reduced hepatic lipid peroxidation products by 68% as compared with the bile-duct ligated group (p<0.05). Liver fatty acid binding protein likely has important antioxidant function during hepatocellular oxidative stress.
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PMID:Expression and antioxidant function of liver fatty acid binding protein in normal and bile-duct ligated rats. 1729 45

Liver grafts are frequently discarded due to steatosis. Steatotic livers can be classified as suboptimal and deteriorate rapidly during hypothermic static preservation, often resulting in graft nonfunction. Hypothermic machine perfusion (MP) has been introduced for preservation of donor livers instead of cold storage (CS), resulting in superior preservation outcomes. The aim of this study was to compare CS and MP for preservation of the steatotic donor rat liver. Liver steatosis was induced in male Wistar rats by a choline-methionine-deficient diet. After 24 hours hypothermic CS using the University of Wisconsin solution (UW) or MP using UW-Gluconate (UW-G), liver damage (liver enzymes, perfusate flow, and hyaluronic acid clearance) and liver function (bile production, ammonia clearance, urea production, oxygen consumption, adenosine triphosphate [ATP] levels) were assessed in an isolated perfused rat liver model. Furthermore, liver biopsies were visualized by hematoxylin and eosin staining. Animals developed 30 to 60% steatosis. Livers preserved by CS sustained significantly more damage as compared to MP. Bile production, ammonia clearance, urea production, oxygen consumption, and ATP levels were significantly higher after MP as compared to CS. These results were confirmed by histology. In conclusion, MP improves preservation results of the steatotic rat liver, as compared to CS.
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PMID:Preservation of steatotic livers: a comparison between cold storage and machine perfusion preservation. 1739 43

A patient with recurrent episodes of hyperammonaemia (highest ammonia level recorded 229 micromol/L, normal 9-33) leading to altered levels of consciousness was diagnosed with partial N-acetylglutamate synthase (NAGS) deficiency (9% residual activity) at age 5 years and was treated with ammonia-conjugating agents (Ucephan 250 mg/kg per day and later sodium phenylbutyrate 200-250 mg/kg per day) for 15 years. A chronically low serum carnitine level (pretreatment plasma free carnitine 4 nmol/L, normal 37 +/- 8 nmol/L; total carnitine 8 nmol/L, normal 46 +/- 10) was assumed to be secondary and was treated with supplemental carnitine (30-50 mg/kg per day). Hypoglycaemia (blood sugar 35 mg/dl, normal 70-100), cardiomegaly, and fatty liver were also noted at diagnosis. The patient died unexpectedly at age 20 years. In retrospect, it was learned that the patient had stopped his carnitine without medical consultation several weeks prior to his death. Additional molecular investigations identified two mutations (R254X and IVS3 + 1G > A) in the patient's OCTN2 (SLC22A5) gene, consistent with a diagnosis of primary carnitine deficiency due to carnitine transporter defect. R245X is a founder mutation in Southern Chinese populations. It is unknown whether the original NAGS deficiency was primary or secondary, but molecular analysis of the NAGS gene failed to identify mutations. Urea cycle enzyme expression may be affected by fatty acid suppression of an AP-1 binding site in the promoter enhancer region of the urea cycle gene. Regardless, it is clear that the NAGS abnormality has led to delay of recognition of the OCTN2 defect, and modified the clinical course in this patient.
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PMID:Deficiency of the carnitine transporter (OCTN2) with partial N-acetylglutamate synthase (NAGS) deficiency. 1770 73


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