Cholestasis ; complications ; metabolism ; therapy ; Cholestasis, Intrahepatic ; etiology ; metabolism ; therapy ; Humans

Bile ; Cholestasis ; etiology ; metabolism ; Humans

Bile ; metabolism ; Cholestasis ; metabolism ; pathology ; Humans

Cholestasis ; metabolism ; Humans ; NF-kappa B ; metabolism ; Pneumonia ; metabolism ; Toll-Like Receptor 4 ; metabolism

Cholestatic liver diseases are characterized by impairments of bile flows and accumulations of biliary constituents such as bile acids and bilirubin. The changes of phase I and II metabolism and the hepatobiliary transport system minimize cholestatic liver injury. These adaptive responses are transcriptionally regulated by several nuclear receptors. Recent studies have revealed that the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are key nuclear receptors for regulating many of the adaptive responses noted in cholestasis. PXR and CAR coordinately regulate not only bile acid metabolism and transport, but also bilirubin clearance. PXR and CAR ligands may be useful in the future for the treatment of cholestatic liver disease.
Transcription Factors/metabolism/*physiology ; Receptors, Steroid/metabolism/*physiology ; Receptors, Cytoplasmic and Nuclear/metabolism/*physiology ; Humans ; Cholestasis/metabolism/*physiopathology

OBJECTIVETo explore the expression level of corticotropin-releasing hormone receptor type-1 (CRHR-1) in intrahepatic cholestatic placental (ICP) tissue.

METHODSHuman placental samples were collected from 10 ICP patients and 10 healthy controls after parturition at 37-40 weeks of gestation. CRHR-1 protein and mRNA expression was assessed by western blotting and nested-real-time fluorescence quantitative PCR, respectively. Normally distributed data were summarized as mean +/- standard deviation, and intergroup comparisons were made by two-tailed Student's t-test. Non-normally distributed data were presented as median with interquartile range, and intergroup comparisons were made by Wilcoxon test. For all statistical analyses, a two-tailed P-value of less than 0.05 was considered statistically significant.

RESULTSThe CRHR-1 fluorescence intensity was lower in ICP tissues (1.55 +/- 0.28) than in placental tissues from healthy controls (1.60 +/- 0.37), but the difference did not reach statistical significance (t = 0.349, P = 0.732). The CRHR-1 mRNA content was slightly higher in the ICP tissues [0.139(0.268)] than in the placental tissues from healthy controls [0.031(0.245)], but the difference did not reach statistical significance (t = 1.504, P = 0.136).

CONCLUSIONCRHR-1 expression is decreased in ICP tissues, which may lead to a smaller volume of placental lobular villi vessels and restrict the CRH positive feedback loop, ultimately promoting acute hypoxic stress and possible harm to the fetus.

Adult ; Case-Control Studies ; Cholestasis, Intrahepatic ; metabolism ; Female ; Humans ; Liver Cirrhosis, Biliary ; metabolism ; Placenta ; metabolism ; Pregnancy ; Pregnancy Complications ; metabolism ; Receptors, Corticotropin-Releasing Hormone ; metabolism

Animals ; Animals, Newborn ; Bile ; metabolism ; Cholestasis, Intrahepatic ; blood ; metabolism ; Female ; Interleukin-6 ; blood ; metabolism ; Male ; Rabbits ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo improve the diagnosis and management of primary biliary cirrhosis (PBC).

METHODSClinical data of 22 cases of PBC were reviewed including the clinical manifestation, laboratory test, and the response to therapy.

RESULTSThere were 20 female patients with an average of 50 years old in total of 22 PBC patients. The major symptoms were pruritus, fatigue, anorexia, and abdominal discomfort. The major signs included jaundice, hepatomegaly, splenmegaly, and ascites. Very high levels of serum alkaline phosphatase (ALP) and serum gamma glutamyl transpeptidase (GGT), hyperbilirubinemia and hypergammaglobulinemia were also detected in most of the patients. The aminotransferase level was only slightly elevated but the AST/ALT ratio was reversed. It took 8 months (ranging from 2 months to 5 years) to confirm the diagnosis after the clinical manifestation onset. Ursodeoxycholic acid could decrease the serum levels of ALP and bilirubin in 80% of the patients (12/15) and improve the symptom of pruritus and fatigue in 72.7% of the patients (11/15).

CONCLUSIONSPBC mainly affects middle-aged women and the main clinical manifestations are hepatosplenomegaly, jaundice, pruritus, and fatigue. Liver function test typically reveal a cholestatic pattern accompanied by hypergammagloblinemia and a positive antimitochondrial antibody (AMA) including M2 subtype (AMA-M2). Ursodeoxycholic acid could improve the abnormal liver function tests and clinical features in PBC patients

Alkaline Phosphatase ; Bilirubin ; Cholestasis ; Female ; Hepatomegaly ; Humans ; Liver Cirrhosis, Biliary ; metabolism ; physiopathology ; Liver Function Tests ; Male ; Middle Aged ; Ursodeoxycholic Acid

The simultaneous administration of two or more drugs may result in interactions that increase or decrease the intended effects of one or both drugs. These interactions are often the result of induced alterations in the metabolism of the drugs. A wide variety of unrelated chemical agents are also capable of enhancing the activity of drug-metabolizing enzymea in the smooth-surfaced endoplasmic reticulum of the liver, and this accelerated metabolism alters the duration and intensity of action of a variety of pharmacological agents. Phenobarbital is a well known drug which promotes the metabolism of durgs in the liver. Some volatile or intravenous anesthetics were reported that enhance hepatic microspmal metabolism for themselves or for other drugs. Of these, Chang and Glazko (1974) reported that ketamine pretreatment did not influence the demethylation rate of drug metabolism and the liver weight in rats. However many opposite opinions have been expressed that ketamine enhanced mierosomal drug metabolism. Marietta et al (1975 and 1976) reported that the demethylating enzyme fraction of the ketamine-pretreated group was double of that of the control group in vitro. Thus we have made a study to evaluate the enhancement of drug metabolism induced by ketamine hydrochloride. Our experimental mice were divided into 4 groups, preteated with saline, phenobarbital, ketamine or carbon tetracbloride for 3 days. On the 1 st, 3 rd, 5th, 7th and 14th day after the pretreatment, we selected 10 mice randomly in each group, and hexobarbital(100mg/kg) was administered intraperitonealy. Then we evaluated the sleeping time, liver weight and microscopic findings of liver tissue. The results are as follows: 1) On the 1 st, 3 rd and 5th day after the pretreatment, the duration of hexobarbital induced hypnosis was significantly shorter in the ketamine-pretreated group than that in the control group, but not as long as that in the phenobarbital-pretreated group. 2) There was no remarkable change of the liver weight in the ketamine pretreated group. On the 1st and 3rd day after the pretreatment, liver weight was significanty increased in the phenobarbital and carbon tetrachloride pretreated groups. 3). Microscopic findings of liver showed no remarkable change in the ketamine-pretreated group, but there were significant cholestasis and hydrophic degeneration in the phenobarbital-and carbon tetrachloride-pretreated group respectively. In conclusion, it may be indicated that ketamine enhances hepatic microsomal drug metabolism because of shortening of the duration of hexobarbital-induced hypnosis.
Anesthetics, Intravenous ; Animals ; Carbon ; Carbon Tetrachloride ; Cholestasis ; Endoplasmic Reticulum ; Hexobarbital ; Hypnosis* ; In Vitro Techniques ; Ketamine ; Liver ; Metabolism ; Mice ; Phenobarbital ; Rats

The modulatory role of bcl-2 gene in hepatocellular apoptosis of rats with glycochenodeoxycholate (GCDC)-induced obstructive jaundice was investigated. The hepatocytes in normal rats and those with bile duct-ligation for 7 days, 14 days and 21 days were isolated and obtained by in situ collagenase perfusion and primary culture. The expression of bcl-2 mRNA in the hepatocytes was detected by RT-PCR. Primary culture was performed on the hepatocytes from normal rats and those with bile duct-ligation for 14 days. 100 mumol/L GCDC was added to the hepatocytes for incubation for 24 h. The hepatocellular apoptotic ratio was measured by using FCM and hepatocellular apoptosis detected in situ by using TUNEL technique. Results showed that the expression of bcl-2 mRNA was not detectable in the hepatocytes of normal rats by RT-PCR technique, while detectable in the hepatocytes of those with bile duct ligation (BDL) for 7, 14 and 21 days. Hepatocellular apoptosis in the BDL group was obviously decreased as compared with normal control group after addition of 100 mumol/L GCDC to the cells for 24 h. It was concluded that the hepatocytes in the BDL rats expressed bcl-2. During obstructive jaundice, expression of bcl-2 from the hepatocytes can inhibit the bile salt-induced hepatocellular apoptosis.
Animals ; Apoptosis ; Cholestasis, Extrahepatic ; chemically induced ; metabolism ; pathology ; Glycochenodeoxycholic Acid ; Hepatocytes ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Wistar