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)

A sensitive radioimmunoassay for cholylglycine, chenodeoxycholylglycine, deoxycholylglycine, and sulfolithocholylglycine was established using antibodies obtained from rabbits injected with albumin conjugates of these bile acids. Glycine-conjugated bile acid levels were measured in sera from 25 control subjects and 110 patients who had hepatic disease (alcoholic cirrhosis, hepatitis, cholestasis, and hepatic malignancy). Sulfolithocholylglycine was elevated in the sera of all 110 patients with hepatic disease. Cholylglucine was within normal range in only three. Chenodeoxycholylglycine was elevated in most sera of patients who had hepatitis, cholestasis, or hepatic malignancy. It was normal in most sera of patients who had alcoholic cirrhosis, suggesting that chenodeoxycholic acid may be subject to further biotransformations in these patients. Deoxycholylglycine was elevated in a minority of patients, none of whom had cholestasis. The data suggest that serum bile acids, particularly sulfolithocholylglycine, are a highly sensitive index for hepatic dysfunction.
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PMID:Levels of immunoreactive glycine-conjugated bile acids in health and hepatobiliary disease. 98 91

Glycoconjugate distribution on rat gut mucosa has been studied by using peroxidase-labelled lectins (Lotus tetragonolobus, Dolichos biflorus, Arachis hypogaea and Glycine max) after surgical interruption of the common bile duct. Specimens from cholestatic rats were compared with sham-operated (simple laparotomy) and normal controls to determine which of the observed modifications could be due either to the operation itself or to the cholestasis. Most of the modifications occurred in the duodenum. The operation itself modified some binding properties. Lotus tetragonolobus binding extended both in cholestatic and in sham-operated rats, but returned to normal levels earlier in sham-operated than in cholestatic rats. Conversely, cholestasis induced (1) almost total loss of Arachis hypogaea binding in the Golgi zone of superficial duodenal goblet cells; (2) an increase at the 14th postoperative day of Dolichos biflorus binding in the cytoplasmic calyx of goblet cells which then diminished up until the 28th day; and (3) an increase of Glycine max binding in the Golgi zone of goblet cells.
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PMID:Modification of lectin binding in rat gut mucosa during experimental cholestasis. 129 62

Non-sulfated bile acid levels including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), five taurine conjugates, and five glycine conjugates in duodenal juice were measured in 50 Chinese infants with cholestasis to test their diagnostic value. All 17 with biliary atresia (BA) cases, 11 out of 26 neonatal hepatitis (NH) cases and one case with paucity of the interlobular bile duct were without detectable bile acids. In those NH patients with detectable bile acids, the major components were conjugated forms of CA and CDCA, which was similar to all 6 cases of the comparison group with other diseases. The minor bile acid components identified in them were glycine conjugated UDCA, free CDCA, free CA, and free and conjugated DCA. Only one patient with NH had taurine conjugated LCA. The mean total duodenal bile acid level in 15 patients with NH was significantly lower than that in the 6 patients of the comparison group. Most patients with NH had a CDCA/CA ratio of less than one, indicating that cholic acid is the predominant form in their bile. Glycine conjugated bile acids were the predominant bile acids present in 11 out of 15 patients with NH and 4 out of 6 of the comparison group patients. The results suggest that the detection of duodenal bile acids by a sensitive HPLC method is of limited value in making a differential diagnosis between BA and NH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of duodenal bile acids by high performance liquid chromatography in infants with cholestasis. 168 Sep 88

Aluminum contaminates components of intravenous nutrient solutions and accumulates in the liver with parenteral feeding. Abnormalities in hepatic function associated with aluminum accumulation include increased serum bile acid concentration and glucuronyl transferase activity and reduced mixed function oxidase levels and bile flow. Whether there are other biochemical responses of the liver to aluminum is unclear. We report the effects of aluminum administration on bile acid conjugation in rats given aluminum intravenously as follows: group I, 1 mg/kg/day for 14 days; group II, 5 mg/kg/day for 14 days; and group III, 5 mg/kg/day for 7 days. Taurine-conjugated bile acids were reduced and glycine/taurine elevated in all groups compared with pair-fed controls. Glycine/taurine was greater in group II versus III and varied directly with serum bile acid concentration. These findings suggest that aluminum administration is associated with decreased taurine conjugation of bile acids, a phenomenon that may be associated with cholestasis.
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PMID:Altered glycine and taurine conjugation of bile acids following aluminum administration to rats. 261 24

Urinary, biliary and serum bile acids were studied in three patients before and after percutaneous transhepatic drainage for total bile duct obstruction. Before drainage high urinary excretion of ten different bile acids occurred. The percentage distribution was: cholic and chenodeoxycholic acid (66-86%), hyocholic (3-16%), 3 beta, 12 alpha-dihydroxy-5-cholenoic (3-6%) and 3 beta-hydroxy-5-cholenoic acid (2-8%). These acids were regularly found in serum. In addition small amounts (less than 2%) of norcholic, allocholic, 3 beta, 7 alpha-dihydroxy-5 beta-cholanoic, 3 alpha, 7 alpha-dihydroxy-5 alpha-cholanoic and lithocholic acid were excrete in urine. Trace amounts of these bile acids were found in serum. After start of drainage biliary bile acid excretion increased rapidly during the first day, dropped to a minimum during the second or third day and then slowly increased again. In spite of normal volumes of bile produced, the total serum bile acids and the urinary excretion of bile acids remained increased during a drainage period of 19 days. The bile acids were of the same type as observed during cholestasis. In serum the increase was mainly due to high concentrations of chenodeoxycholic and 3 beta-hydroxy-5-cholenoic acid, as sulphate esters. Glycine and taurine conjugates of cholic, chenodeoxycholic and hyocholic acid were mainly excreted in bile. Bile acid sulphate esters were only present in trace amounts in bile and were mainly excreted in urine. This, combined with low renal clearance, explains the elevated serum levels of sulphate esters of chenodeoxycholic and 3 beta-hydroxy-5-cholenoic acid conjugates.
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PMID:Bile acid synthesis and excretion following release of total extrahepatic cholestasis by percutaneous transhepatic drainage. 677 67

A chromatographic separation of glucuronidated bile acids using the anion exchanger diethylaminohydroxypropyl Sephadex LH-20 (DEAP LH-20) is described. Group separation of non-sulfated, non-glucuronidated bile acids, bile acid glucuronides, bile acid monosulfates, and bile acid disulfates was obtained. The method allowed analysis of all these bile acid derivatives in the urine of 15 patients with cirrhosis of the liver and cholestasis. The patients excreted in mean 30.4 mumol/24 h non-sulfated, non-glucuronidated bile acids, 90.3 mumol bile acid monosulfates, and 10.2 mumol bile acid glucuronides. Glycine- or taurine-conjugated were 68% of the non-sulfated, non-glucuronidated bile acids, 96% of bile acid sulfates, and 81% of bile acid glucuronides.
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PMID:Analysis of bile acid glucuronides in urine: group separation on a lipophilic anion exchanger. 711 46

Endogenous opioids, including methionine enkephalin, have been implicated in the control of adrenocorticotrophic hormone release by acting through mu-opiate receptors in the hypothalamus. Recently, alterations in the central opioid system have been postulated to occur in cholestasis. In addition, alterations in hypothalamic corticotropin-releasing hormone content and messenger RNA levels, as well as basal release, have been described in bile duct-resected rats, and hypothalamic methionine enkephalin is colocalized with corticotropin-releasing hormone in hypothalamic neurons. Therefore hypothalamic and pituitary methionine enkephalin content and hypothalamic proenkephalin messenger RNA levels, as well as hypothalamic mu-opiate receptor-mediated responses in vitro and in vivo, were studied in rats with acute cholestasis caused by bile duct resection and in respective controls. Hypothalamic and pituitary methionine enkephalin levels were similar in bile duct-resected, sham-resected and unoperated control rats. In addition, hypothalamic proenkephalin steady state messenger RNA levels were similar in the three groups of animals. mu-Opiate receptor stimulation of hypothalamic explants in vitro with the specific mu-opiate receptor agonist ligand [D-Ala2,N-Me-Phe4,Gly-ol]-Enkephalin resulted in 8.2% and 16.9% inhibition of corticotropin-releasing hormone release in sham-resected and unoperated control rats, respectively. In contrast, treatment of hypothalamic explants from bile duct-resected rats with [D-Ala2,N-Me-Phe4,Gly-ol]-Enkephalin resulted in a significant 22.5% increase in corticotropin-releasing hormone release. Systemic administration of the mu-opiate receptor agonist morphine to rats in vivo resulted in significantly higher incremental rises in plasma adrenocorticotropic hormone levels in sham-resected and unoperated control animals than in bile duct-resected rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in hypothalamic mu-opiate receptor-mediated responses but not methionine enkephalin or proenkephalin messenger RNA levels in rats with acute cholestasis. 807 27

The opiate withdrawal-like reaction experienced by patients with cholestatic liver disease after the ingestion of the opiate antagonist nalmefene led to the hypothesis that increased opioidergic neurotransmission/neuromodulation in the central nervous system (CNS) contributes to the pathophysiology of cholestasis. The state of antinociception, which is stereospecifically reversed by naloxone, documented in rats with cholestasis from bile duct resection supports this hypothesis. To further study the opioid system in this animal model of cholestasis, we studied the release of endogenous opioid peptides into the extracellular fluid of the dorso-lateral striatum by the technique of in-vivo microdialysis. Total opioid peptide concentration in the dialysate was measured by a solid phase radioimmunoassay with an antibody directed against the N-terminus of the Tyr-Gly-Gly-Phe-X amino acid sequence after acetylation. Basal total opioid peptide release was significantly higher after surgery in both sham resected and bile duct resected animals. However, basal (unstimulated) total opioid peptide release in the striatum of rats was not altered by cholestasis. It is inferred that the opioidergic abnormalities of cholestasis are not associated with an appreciable increase in the release of endogenous opioids into the extracellular fluid of the striatum. Abnormal processing of specific opioid peptides in cholestasis however, cannot be excluded.
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PMID:Basal total opioid peptide release in the striatum of rats with cholestasis from bile duct resection: a study by the use of in vivo microdialysis. 931 7

In chronic viral hepatitis, autoimmune hepatitis, and some chronic cholestatic liver diseases, T-lymphocytes serve as effector cells of the immunostimulatory processes. Cellular interactions of immune cells with extracellular matrix (ECM) components are regulated primarily via the beta 1 subfamily of integrin receptors. The target epitope of several such integrin receptors is the Arg-Gly-Asp (RGD) sequence, a cell adhesion motif shared by several matrix-associated adhesive glycoproteins. We review the use of synthetic nonpeptidic analogues of RGD and of soluble receptor of tumor necrosis factor (TNF)-alpha in the prevention of immune-mediated, concanavalin A-induced liver damage in mice and of RGD analogues in inhibiting the development of liver cirrhosis in rats. The concanavalin A-induced elevation of serum transaminases and TNF-alpha, and the infiltration of liver tissue by inflammatory cells, were inhibited by pretreatment of the mice with the synthetic RGD mimetics and soluble TNF receptor. In rats, the progression of thioacetamide-induced liver cirrhosis was markedly inhibited by the coadministration of the RGD mimetic SF-6,5. The compounds described here may be examined therapeutically for pathological conditions in the liver, manifested as necroinflammation, cholestasis and fibrosis.
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PMID:The use of synthetic analogues of Arg-Gly-Asp (RGD) and soluble receptor of tumor necrosis factor to prevent acute and chronic experimental liver injury. 962 59

Cholestasis results in the accumulation of cytotoxic bile acids in the body. The cytoprotective effect of S-adenosylmethionine (SAMe) and cAMP were compared in two in vitro models of bile acid-induced apoptosis. Primary cultures of rat hepatocytes and canine renal tubular cells (Madin-Darby canine kidney [MDCK] cells stably transfected with the conjugated bile salt transporter, sodium [Na+]/taurocholate cotransporting polypeptide [Ntcp]) were treated with conjugated bile acids and monitored for apoptosis. Glycine-conjugated bile acids caused similar amounts of apoptosis, whereas taurine-conjugated bile acids were five to 10 times more toxic in MDCK-Ntcp cells than in hepatocytes. Treatment with the 1,4-butanedisulfonate salt of SAMe (500 microM) or the stable chlorophenylthio-cAMP analogue (100 microM) inhibited bile acid-induced apoptosis in hepatocytes by 70% and 40%, respectively. In MDCK-Ntcp cells, SAMe inhibited apoptosis by 20%, but cAMP was without effect. Immunoblotting for activation of putative survival kinases in cAMP-treated cells (phosphorylated protein kinase B [Akt] or mitogen-activated protein kinase [MAPK]) was done using phosphospecific antibodies. cAMP increased Akt phosphorylation threefold in hepatocytes but not in MDCK-Ntcp cells. Activation of p42/p44 MAPK was inhibited by cAMP in both cells. SAMe protects against bile acid-induced apoptosis in hepatocytes and MDCK-Ntcp cells. The cytoprotective effect of cAMP is seen only in hepatocytes and may reflect tissue-specific activation of Akt.
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PMID:S-adenosylmethionine and cAMP confer differential cytoprotection against bile acid-induced apoptosis in canine renal tubular cells and primary rat hepatocytes. 1258 85


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