Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serological tests may be of value in differentiating acute and chronic bile duct obstruction because the rate of alteration of hepatic cellular integrity and function will affect the rate of cellular product release. In a canine model the common bile duct was obstructed either suddenly (N = 7) or gradually (N = 5). A control group (N = 5) had the common bile duct dissected free from the surrounding tissues. Blood was taken before and 1, 2, 4, 7, 11, 14, 17, 21, and 28 days after initiating obstruction. Serum alkaline phosphatase, bilirubin, aspartate aminotransferase, alanine aminotransferase, ornithine carbamyl transferase, and gamma-glutamyl transferase levels were significantly greater with sudden compared to gradual occlusion, and the values were larger than those in the control. The range of values of alkaline phosphatase, bilirubin, and aspartate aminotransferase did not overlap in the acute and chronic groups at specific times. Serum albumin and total protein were normal in all groups. The magnitude of alkaline phosphatase, aspartate aminotransferase, and bilirubin elevation may help in the differentiation of acute and chronic biliary obstruction.
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PMID:Diagnostic value of liver function tests in bile duct obstruction. 256 54

Changes in the levels of urea cycle enzymes and polyamine metabolism in the liver of rats treated with alpha-naphthylisothiocyanate (ANIT), an inducer of experimental cholestasis, were studied. Activities of arginase increased approximately two-fold compared to the control values during the period of 24-72 hours after oral administration of ANIT (100 mg/kg), while activities of ornithine carbamyltransferase and ornithine aminotransferase decreased. The activity of ornithine decarboxylase was elevated by approximately 20- and 10-fold at 12 and 60 hours, respectively, after ANIT administration. Putrescine concentration doubled 24-48 hours after the ANIT administration, but spermidine level rose more slowly and reached the level of 1.5-fold of the control level in 36-72 hours. Spermine concentration decreased initially but increased in 96 hours. These results suggest that the increased activity of urea cycle accounts for the increase in the ornithine content and that the putrescine and spermidine acts as the initiator of recovery of the liver damaged by ANIT treatment.
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PMID:Changes in polyamine metabolism in rat liver after oral administration of alpha-naphthylisothiocyanate. 372 14

Serum ornithine carbamyl transferase (OCT) was evaluated on eighteen dogs. Three groups were used, the first and second ones were treated with carbon tetrachloride (CCI(4)) to produce acute hepatic necrosis and cirrhosis. To the third group a ductus choledochus ligation was performed to simulate extrahepatic cholestasis. Ornithine carbamyl transferase has proven its use in all phases of hepatic necrosis, but only after the fourth day in the extrahepatic cholestasis. Finally in cirrhosis, it was sometimes difficult to interpret the results.
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PMID:[Serum ornithine transcarbamylase (OCT) activity in experimental liver diseases in the dog]. 424 89

Mitochondrial enzymes in rat livers or intestines were investigated in experimental models with ethanol- or other hepatotoxic agent-induced liver injuries and extrahepatic cholestasis. In clinical experiment, activities of mitochondrial GOT (mGOT) and ornithine carbasmyl transferase (OCT) were examined in alcoholisms and patients with other various liver diseases. Results obtained are as follows; 1) The activities of OCT and mGOT were increased particularly at onset of acute hepatitis, in chronic active hepatitis and intrahepatic cholestasis, showing that mitochondria were injured strikingly in these diseases. The activities in alcoholics were not so great, however mGOT/total-GOT ratio was increased in level than in other diseases. 2) Changes in mitochondrial enzymes of rat liver treated with ethanol were too varied to catch the actual tendency in this pathologic state. 3) Administration of galactosamine, carbon tetrachloride, or alpha-naphthyl isothiocyanate (ANIT) caused a significant fall in activities of succinate cytochrome C reductase and OCT, along with increase in serum activity of OCT, indicating severe mitochondrial injury with these drugs. Extrahepatic cholestasis following bile duct ligation showed the same changes of mitochondrial enzymes in liver tissue and serum. 4) These data indicate that observation of activities of serum OCT, mGOT, along with mGOT/total-GOT ratio are useful for estimation of mitochondrial damage in extra- and intra-hepatic cholestasis, and acute or chronic active hepatitis. The changes in alcoholic fatty liver was not so subtle as compared with other liver diseases. 5) It is surmized that smooth endoplasmic reticulum was increased in content and pentose phosphate shunt was inhibited by chronic ethanol treatment, estimating from increased activities of NADH-ferricyanide reductase and gamma-glutamyl transpeptidase, and decreased activity of glucose-6-phosphate dehydrogenase. 6) The changes in hepatic enzymes with ethanol treatment were paralleled with those of intestinal ones, indicating that metabolic changes in intestine contribute someway in the formation of alcoholic fatty liver. 7) Chronic ethanol treatment induced lowered active transport in intestinal mucosa, which indicates inhibition in absorption of various nutrients by ethanol.
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PMID:[Experimental and clinical studies on enzymes of mitochondria in various liver diseases; with special reference to alcoholic liver disease (author's transl)]. 625 Sep 59

Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) shows diverse metabolic abnormalities such as urea cycle dysfunction together with citrullinemia, galactosemia, and suppressed gluconeogenesis. Such abnormalities apparently resolve during the first year of life. However, metabolic profiles of the silent period remain unknown. We analyzed oxidative stress markers and profiles of amino acids, carbohydrates, and lipids in 20 asymptomatic children with aspartate/glutamate carrier isoform 2-citrin-deficiency aged 1-10 years, for whom tests showed normal liver function. Despite normal plasma ammonia levels, the affected children showed higher blood levels of ornithine (p<0.001) and citrulline (p<0.01)--amino acids involved in the urea cycle--than healthy children. Blood levels of nitrite/nitrate, metabolites of nitric oxide (NO), and asymmetric dimethylarginine inhibiting NO production from arginine were not different between these two groups. Blood glucose, galactose, pyruvate, and lactate levels after 4-5h fasting were not different between these groups, but the affected group showed a significantly higher lactate to pyruvate ratio. Low-density and high-density lipoprotein cholesterol levels in the affected group were 1.5 times higher than those in the controls. Plasma oxidized low-density lipoprotein apparently increased in the affected children; their levels of urinary oxidative stress markers such as 8-hydroxy-2'-deoxyguanosine and acrolein-lysine were significantly higher than those in the controls. Results of this study showed, even during the silent period, sustained hypercitrullinemia, hypercholesterolemia, and augmented oxidative stress in children with citrin deficiency.
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PMID:Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin-deficiency even during the silent period. 1923 6

There are limited data regarding donor hepatocyte engraftment into recipient liver after human hepatocyte transplantation (HHTx). We reviewed the explant livers of seven children with metabolic disorders [ornithine-transcarbamylase deficiency (one), coagulation factor VII deficiency (three), Crigler-Najjar syndrome (one), progressive familial intrahepatic cholestasis type 2 (PFIC-2) deficiency (two)] who received allograft hepatocytes by intraportal infusion with improvement in phenotype, although all later underwent liver transplantation (LT). Immunohistochemistry for bile salt export protein (BSEP) in the PFIC-2 patients and genetic typing following laser capture microdissection (LCM) of liver cells in the others were used to identify donor hepatocytes in recipient explant livers. Explant livers usually showed a preserved lobular architecture. In one patient, hepatocytes were identified inside portal vein thrombi. No donor hepatocytes in liver cell plates were identified immunohistochemically or by genetic typing. HHTx was generally followed by partial recovery of metabolic function; the procedure was well tolerated; any increase in portal vein pressure was transient. Hepatocytes were identified in portal vein thrombi, even months after portal vein infusion. Further studies are needed to monitor donor hepatocytes in vivo, to quantify better the efficacy of the procedure and to find ways of improving engraftment and function.
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PMID:Liver after hepatocyte transplantation for liver-based metabolic disorders in children. 1936 77

Hyperargininemia is a rare inborn error of metabolism due to arginase deficiency, which is inherited in an autossomal recessive manner. Arginase is the final enzyme of the urea cycle and catalyzes the conversion of arginine to urea and ornithine. This condition typically presents in early childhood (between 2 and 4 years of age) with developmental delay associated with progressive spastic paraparesis. Neonatal presentation is very uncommon with a poorly described outcome. Here, we discuss two cases of neonatal cholestasis as initial clinical presentation of hyperargininemia. In case 1, diagnosis was established at 2 months of age upon investigation of the etiology of cholestatic injury pattern and hepatosplenomegaly, and treatment was then initiated at when the patient was 3 months old. Unfortunately, the patient had progressive biliary cirrhosis to end-stage liver disease complicated with portal hypertension for which she underwent successful orthotopic liver transplant at 7 years of age. In case 2, hyperargininemia was identified through newborn screening and treatment was started when patient was 21 days old. Cholestasis was only identified in the patient's further evaluation and it resolved 2 weeks into treatment. The patient is currently 18 months old and her development and neurological examination remain unremarkable. Neonatal cholestasis as first presentation of hyperargininemia is rare, but this disorder should be included in the differential diagnosis of unexplained cholestasis in the neonate. In fact, these two cases suggest that arginase deficiency may be the cause of cholestatic liver disease.
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PMID:Neonatal cholestasis: an uncommon presentation of hyperargininemia. 2122 17

Argininemia is a rare hereditary disease due to a deficiency of hepatic arginase, which is the last enzyme of the urea cycle and hydrolyzes arginine to ornithine and urea. The onset of the disease is usually in childhood, and clinical manifestations include progressive spastic paraparesis and mental retardation. Liver involvement is less frequent and usually not as severe as observed in other UCDs. For this reason, and because usually there is a major neurological disease at diagnosis, patients with argininemia are rarely considered as candidates for OLT despite its capacity to replace the deficient enzyme by an active one. We report on long-term follow-up of two patients with argininemia. Patient 1 was diagnosed by the age of 20 months and despite appropriate conventional treatment progressed to spastic paraparesis with marked limp. OLT was performed at 10 years of age with normalization of plasmatic arginine levels and guanidino compounds. Ten years post-OLT, under free diet, there is no progression of neurological lesions. The second patient (previously reported by our group) was diagnosed at 2 months of age, during a neonatal cholestasis workup study. OLT was performed at the age of 7 years, due to liver cirrhosis with portal hypertension, in the absence of neurological lesions and an almost-normal brain MRI. After OLT, under free diet, there was normalization of plasmatic arginine levels and guanidino compounds. Twelve years post-OLT, she presents a normal neurological examination. We conclude that OLT prevents progressive neurological impairment in argininemia and should be considered when appropriate conventional treatment fails.
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PMID:Liver transplantation prevents progressive neurological impairment in argininemia. 2355 24