Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intrahepatic cholestasis associated with severe extrahepatic bacterial infection is well recognized in humans. A similar syndrome is not well characterized in veterinary medicine. Five dogs with severe extrahepatic bacterial infection that developed histologically confirmed intrahepatic cholestasis were selected from the authors' case files. The types of infections included pneumonia, peritonitis secondary to a rectal tear, urinary tract infection, bite wounds, and vegetative endocarditis. Escherichia coli was involved in two of the dogs, mixed infection in one dog, and a gram-positive cocci in the other two dogs. Total bilirubin concentrations ranged from 3.5 to 33.5 mg/dl. Serum liver enzyme activities showed only mild to moderate increases: alkaline phosphatase (ALP, 41-750 IU/l), alanine aminotransferase (ALT, 25-235 IU/l), and aspartate aminotransferase (AST, 99-255 IU/l). Fasting serum bile acids concentration was markedly elevated in the one dog in which it was measured (259 mumol/l). Histologically, the cholestasis was characterized by bile pigment accumulation in hepatocytes, canaliculi, and/or Kupffer's cells. Inflammatory parenchymal changes, when present, were minimal. The findings of hyperbilirubinemia, only a slight increase in the liver enzyme activities, and minimal inflammatory changes in liver tissue specimens in the five dogs with extrahepatic bacterial infections are similar to the findings in intrahepatic cholestasis associated with extrahepatic bacterial infection in humans.
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PMID:Cholestasis associated with extrahepatic bacterial infection in five dogs. 258 68

Intrahepatic cholestasis associated with hyperbilirubinemia was induced by the simultaneous administration of ethynyl estradiol (EE) and chlorpromazine hydrochloride (CPZ) for 7 days to female Sprague-Dawley rats. Increases in direct serum bilirubin levels and alkaline phosphatase activities were observed concomitantly with diminished bile flow and bile acid excretion. However, the bilirubin output in the bile remained unchanged. [14C]Erythritol clearance decreased in parallel with the diminished bile flow, while [14C]sucrose biliary clearance increased, suggesting that the decrease in bile flow was of canalicular origin and also due to increased permeability in the biliary tract. There was a prominent decrease in the bile acid-independent flow, and the bile acid-dependent flow also decreased concomitantly with the diminished bile acid excretion. Slight increases in cytochrome P-450 and anilin hydroxylase activities in liver microsomes were observed, and bilirubin UDP-glucuronyl transferase activity increased significantly. Indirect bilirubin clearances determined by a bilirubin load test were markedly reduced in the icteric rats. The bilirubin load test also suggested that bilirubin flowed back into the circulating blood and that gluculonidation of bilirubin mono-gluculonide (BMG) to bilirubin diglucuronide (BDG) was impaired. Light microscopic examinations of the liver revealed marked proliferation of the bile ductules and numerous vacuoles in the hepatocytes. Dilatation of the bile canaliculi with diminished microvilli was also detected by scanning electron microscopy.
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PMID:Intrahepatic cholestasis and hyperbilirubinemia in ethynyl estradiol and chlorpromazine-treated rats. 667 12

Intrahepatic cholestasis with situs inversus of the liver has not been reported in the literature. PURPOSE--A follow-up case for approximately 14 years (by one of the authors, MM). METHODS--Clinical aspects were studied and several laboratory exams as well as three ultrasonography and one computerized tomography exams were performed. Percutaneous and endoscopic cholangiographies were attempted. RESULTS--Four days after the patient was submitted to a surgical replacement of the aortic valve (with extracorporeal circulation), she developed jaundice, severe pruritus, dark urine, and pale stools. Serum levels of bilirubin, alkaline phosphatase, gama-glutamil transferase, and cholesterol were very high. Ultrasonography and computerized tomography exams did not reveal any evidence of extrahepatic obstruction. The tomography exam confirmed the existence of situs inversus in the stomach and liver. We were not successful in performing the cholangiography exams. Clinical and laboratory data as to cholestasis returned to normal after 4 months with no recurrence or complication during the follow-up period (14 years). CONCLUSION--The differential diagnosis between intra and extra-hepatic cholestasis in patients with situs inversus of the liver may be difficult. Therefore it will be necessary to collect clinical data and various complementary exams such as endoscopic retrograde cholangiopancreatography which is very difficult to perform in these patients.
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PMID:[Intrahepatic cholestasis with situs inversus of the liver]. 782 Jan 48

We investigated the therapeutic effect of tauroursodeoxycholate on phalloidin-induced cholestasis in rats. Intrahepatic cholestasis was induced by administration of phalloidin (500 microg/kg, i.p.) for 7 days. From the day of the last phalloidin injection, tauroursodeoxycholate (60-360 micromol/kg) was given intravenously twice a day for 4 days. On the next day after the last tauroursodeoxycholate administration, bile flow, serum biochemical parameters and biliary lipid excretion rates were determined. Tauroursodeoxycholate significantly suppressed the decrease in bile flow and increases in serum alkaline phosphatase, leucine aminopeptidase and glutamic pyruvic transaminase activities, cholesterol, phospholipid and bile acid concentrations observed in phalloidin-induced cholestasis in rats. Furthermore, tauroursodeoxycholate significantly improved the biliary cholesterol and phospholipid excretion rates in phalloidin-induced cholestasis in rats. These results demonstrate the usefulness of tauroursodeoxycholate as a therapeutic agent in intrahepatic cholestasis.
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PMID:Effect of sodium tauroursodeoxycholate on phalloidin-induced cholestasis in rats. 1140 49

Intrahepatic Cholestasis of Pregnancy (ICP) constitutes the most common, reversible liver disease closely connected with pregnancy and spontaneously resolving in puerperium. ICP usually reoccurs in consecutive pregnancies (45-90%), often in a more intensified form. Many compounds (hormones, cytokines, medicines, endotoxins) can impair transport in the hepatocyte, disturb the intracellular transport and increase the permeability of the intercellular connections. As a result, the elements of bile may appear in the peripheral blood. Gestational cholestasis constitutes a classic example of intrahepatic cholestasis. The etiology of ICP is multifactorial with hormonal, genetic and environmental factors participating in the process. The diagnosis is based on the presence of pruritus, elevated values of bile acids in the blood serum and of aminotransferases (aspartic, aminopropionic and gamma-glutamylotranspeptydase (AspAt, AlAt, GGTP)), as well as spontaneous remission in the second or third week after childbirth, of lack of other illnesses causing pruritus and icterus. Clinical and biochemical symptoms of ICP include: pruritus without skin rash (usually after 30 weeks of gestation), mild icterus, steatorrhea etc. Abnormalities in the laboratory tests of the LFT (liver function tests) encompass: an increase in the serum concentration of fatty acids (BA) which can be the first and only laboratory abnormality. Concentrations surpassing 10 micromol/l are considered to be abnormal. Concentration of BA higher than 40 micromol/l allows to recognize a case of severe ICP, connected with the risk of premature delivery presence of the meconium liquor, surgical means of delivery and low APGAR score of the newborn (< 7 pt). In about 80% of pregnant women with ICP, the BA concentration ranges between 10-40 micromol/l, but perinatal results are comparable with uncomplicated pregnancies. Some authors are of the opinion that abnormal AlAt value is the most sensitive test, other authors consider the abnormal values of alkaline phosphatase and bilirubin to be the most pathognomonic factors. Other abnormal tests include: higher activity of alpha-hydroxybutyric dehydrogenase correlated with an increase of the alkaline phosphatase and bilirubin; mild metabolic acidosis; dyslipidemia with elevated concentrations of the total lipids, total cholesterol and free LDL cholesterol and apolipoprotein; abnormal glucose tolerance test. ICP constitutes a medical problem that carries a considerable risk for the fetus, resulting from an increased flow of bile acids to the fetal blood circulation (elevated level in the amniotic fluid, in the umbilical blood serum and meconium). The risk of adverse effects for the fetus correlates with the rise of BA concentration in maternal blood serum. Cholestasis increases the risk of premature labor, presence of meconium in the amniotic fluid, fetal bradycardia, intrauterine asphyxia and stillbirth, particularly when the concentration of serum bile acids on an empty stomach is above 40 micromol/l. However, maternal clinical signs and symptoms do not correlate with the fetal outcome. Aspiration of bile acids or their accumulation in the fetal blood circulation are responsible for the increased frequency of RDS appearing in ICP. The aim of the obstetric management of ICP is to reduce maternal symptoms and biochemical disorders and to minimize the risk of premature delivery fetal distress and sudden death. ICP management should include: bed regime, light, low-fat diet, no stress, upper abdomen ultrasound examination, LFT tests and thrombotic tests once a week, monitoring of the fetal well-being with the available biophysical methods, pharmacotherapy and therapeutic termination of pregnancy in case of serious illness and/or the fetal distress. Ursodeoxycholic acid (UDCA) is the basis of the pharmacological treatment of pregnant women and currently constitutes the most promising treatment option of ICP. UDCA is administered orally in the dosage of 10-16 mg/kg/24, what in practice means 250-300 mg/2-3 times a day.
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PMID:[Clinical practice guidelines of the Team of Experts of the Polish Gynecological Society: management of the intrahepatic cholestasis of pregnancy]. 2334 3

Alcoholic hepatitis (AH) is an acute inflammatory liver disease with poor prognosis. Infections in AH are difficult to detect and contribute to short-term mortality. Intrahepatic cholestasis and elevated alkaline phosphatase levels are also associated with worse outcomes. This report describes an uncommon presentation of severe AH.
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PMID:Severe Alcoholic Hepatitis: Atypical Presentation with Markedly Elevated Alkaline Phosphatase. 2922 8