Skip Nav Destination
Close Modal
Update search
Filter
- Title
- Author
- Author Affiliations
- Full Text
- Abstract
- Keyword
- DOI
- ISSN
- EISSN
- Issue
- Volume
- References
Filter
- Title
- Author
- Author Affiliations
- Full Text
- Abstract
- Keyword
- DOI
- ISSN
- EISSN
- Issue
- Volume
- References
Filter
- Title
- Author
- Author Affiliations
- Full Text
- Abstract
- Keyword
- DOI
- ISSN
- EISSN
- Issue
- Volume
- References
Filter
- Title
- Author
- Author Affiliations
- Full Text
- Abstract
- Keyword
- DOI
- ISSN
- EISSN
- Issue
- Volume
- References
Filter
- Title
- Author
- Author Affiliations
- Full Text
- Abstract
- Keyword
- DOI
- ISSN
- EISSN
- Issue
- Volume
- References
Filter
- Title
- Author
- Author Affiliations
- Full Text
- Abstract
- Keyword
- DOI
- ISSN
- EISSN
- Issue
- Volume
- References
NARROW
Format
Article Type
Date
Availability
1-14 of 14
Keywords: cholestasis
Close
Follow your search
Access your saved searches in your account
Would you like to receive an alert when new items match your search?
Sort by
Articles
Marcelo G. Roma, Flavia D. Toledo, Andrea C. Boaglio, Cecilia L. Basiglio, Fernando A. Crocenzi, Enrique J. Sánchez Pozzi
Journal:
Clinical Science
Clin Sci (Lond) (2011) 121 (12): 523–544.
Published: 22 August 2011
..., and even to extrahepatic ones. Such versatility is the result of its multiple mechanisms of action. UDCA stabilizes plasma membranes against cytolysis by tensioactive bile acids accumulated in cholestasis. UDCA also halts apoptosis by preventing the formation of mitochondrial pores, membrane...
Abstract
UDCA (ursodeoxycholic acid) is the therapeutic agent most widely used for the treatment of cholestatic hepatopathies. Its use has expanded to other kinds of hepatic diseases, and even to extrahepatic ones. Such versatility is the result of its multiple mechanisms of action. UDCA stabilizes plasma membranes against cytolysis by tensioactive bile acids accumulated in cholestasis. UDCA also halts apoptosis by preventing the formation of mitochondrial pores, membrane recruitment of death receptors and endoplasmic-reticulum stress. In addition, UDCA induces changes in the expression of metabolizing enzymes and transporters that reduce bile acid cytotoxicity and improve renal excretion. Its capability to positively modulate ductular bile flow helps to preserve the integrity of bile ducts. UDCA also prevents the endocytic internalization of canalicular transporters, a common feature in cholestasis. Finally, UDCA has immunomodulatory properties that limit the exacerbated immunological response occurring in autoimmune cholestatic diseases by counteracting the overexpression of MHC antigens and perhaps by limiting the production of cytokines by immunocompetent cells. Owing to this multi-functionality, it is difficult to envisage a substitute for UDCA that combines as many hepatoprotective effects with such efficacy. We predict a long-lasting use of UDCA as the therapeutic agent of choice in cholestasis.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (2008) 114 (9): 567–588.
Published: 02 April 2008
... alteration in cholestatic hepatopathies. The present review addresses in detail this new information by summarizing a number of recent experimental findings on the structural, functional and regulatory aspects of hepatocellular transporter function in acquired cholestasis. This comprises (i) a short overview...
Abstract
The recent overwhelming advances in molecular and cell biology have added enormously to our understanding of the physiological processes involved in bile formation and, by extension, to our comprehension of the consequences of their alteration in cholestatic hepatopathies. The present review addresses in detail this new information by summarizing a number of recent experimental findings on the structural, functional and regulatory aspects of hepatocellular transporter function in acquired cholestasis. This comprises (i) a short overview of the physiological mechanisms of bile secretion, including the nature of the transporters involved and their role in bile formation; (ii) the changes induced by nuclear receptors and hepatocyte-enriched transcription factors in the constitutive expression of hepatocellular transporters in cholestasis, either explaining the primary biliary failure or resulting from a secondary adaptive response; (iii) the post-transcriptional changes in transporter function and localization in cholestasis, including a description of the subcellular structures putatively engaged in the endocytic internalization of canalicular transporters and the involvement of signalling cascades in this effect; and (iv) a discussion on how this new information has contributed to the understanding of the mechanism by which anticholestatic agents exert their beneficial effects, or the manner in which it has helped the design of new successful therapeutic approaches to cholestatic liver diseases.
Articles
Noemí M. Atucha, David Iyú, Antonia Alcaraz, Vladimir Rosa, Concepción Martínez-Prieto, M. Clara Ortiz, Juan Antonio Rosado, Joaquín García-Estañ
Journal:
Clinical Science
Clin Sci (Lond) (2007) 112 (3): 167–174.
Published: 03 January 2007
... developed and occurs during the cholestasis phase. Correspondence: Professor Noemí M. Atucha (email ntma@um.es ). 18 8 2006 1 9 2006 1 9 2006 The Biochemical Society 2007 calcium signalling bile-duct ligation capacitative Ca 2+ entry cholestasis liver cirrhosis...
Abstract
In the present study, we have analysed the mechanisms of Ca 2+ entry and release in platelets obtained from BDL (bile-duct-ligated) rats, 11–13 days and 4 weeks after surgery. Platelets were washed and loaded with fura-2, and [Ca 2+ ] i (cytosolic Ca 2+ concentration) was determined in cell suspensions by means of fluorescence spectroscopy. Basal [Ca 2+ ] i was similar in platelets from BDL rats compared with those from their respective controls, both in the absence and presence of extracellular Ca 2+ . Platelet stimulation with thrombin in the absence and presence of extracellular Ca 2+ induced a rapid rise in [Ca 2+ ] i that was of greater magnitude in platelets from BDL rats than in controls. Ca 2+ storage was significantly elevated in platelets from BDL rats, as well as the activity of SERCA (sarcoplasmic/endoplasmic-reticulum Ca 2+ -ATPase). Capacitative Ca 2+ entry, as evaluated by inhibition of SERCA with thapsigargin, was also altered in platelets from BDL rats, having lower rates of Ca 2+ entry. In conclusion, chronic BDL alters intracellular Ca 2+ homoeostasis in platelets, such that an enhanced Ca 2+ release is evoked by thrombin, which may be due to an increased amount of Ca 2+ stored in the intracellular organelles and secondary to an enhanced activity of SERCA. These alterations are already evident before cirrhosis has completely developed and occurs during the cholestasis phase.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (2002) 102 (6): 603–614.
Published: 30 April 2002
... different experimental models of cholestasis. In this review we describe the experimental data generated from this model in our laboratory over a period of years, including application of hepatocyte couplets to the study of cytoskeletal changes within the hepatocyte and mechanisms of hepatoprotection in...
Abstract
Preparations of isolated liver cells, either freshly prepared or in culture, have been available for many years; however, because they lack the polarization of the cell in the tissue, their application to the study of processes involved in bile formation has been very limited. The hepatocyte couplet model offers a unique opportunity to study in vitro the intracellular processes involved: not only the physiology and pathophysiology of bile formation, but also the corresponding structural and molecular disturbances underlying different experimental models of cholestasis. In this review we describe the experimental data generated from this model in our laboratory over a period of years, including application of hepatocyte couplets to the study of cytoskeletal changes within the hepatocyte and mechanisms of hepatoprotection in experimentally induced, clinically relevant models of intrahepatic cholestasis.
Articles
Maria J. PASCUAL, Maria A. SERRANO, Mohamad Y. EL-MIR, Rocio I.R. MACIAS, Felipe JIMÉNEZ, Jose J.G. MARIN
Journal:
Clinical Science
Clin Sci (Lond) (2002) 102 (5): 587–593.
Published: 22 April 2002
... species and progesterone metabolites were measured by GC-MS, in the serum of 411 healthy pregnant women. Samples were collected after an overnight fast in the final week of each trimester of gestation. Two pregnant women were excluded because of the suspicion of intrahepatic cholestasis of pregnancy (ICP...
Abstract
The aim of this study was to identify a subgroup of pregnant women with asymptomatic hypercholanaemia of pregnancy (AHP), in which the relationship between alterations in the level and pattern of serum bile acids (BAs) and of progesterone plus progesterone metabolites could be investigated in the absence of overt impairment of hepatobiliary function. Cholanaemia and serum concentrations of progesterone were assayed by an enzymic technique and by ELISA respectively, while BA molecular species and progesterone metabolites were measured by GC-MS, in the serum of 411 healthy pregnant women. Samples were collected after an overnight fast in the final week of each trimester of gestation. Two pregnant women were excluded because of the suspicion of intrahepatic cholestasis of pregnancy (ICP). Cholanaemia was found to increase progressively throughout pregnancy, but with normal mean values lower than 3.0 μ M. Thus in our series AHP was defined arbitrarily as the presence of serum total BA concentrations 2-fold higher than this value, i.e. 6 μ M, in the absence of hepatobiliary disease or symptoms of ICP. The prevalence of this condition was observed to increase with gestational age. Changes in the pattern of serum BAs in AHP were also found. These were reflected in a marked increase in the proportion of cholic acid together with a decrease in that of deoxycholic acid, while the proportions of chenodeoxycholic acid and lithocholic acid changed only moderately. When groups at the same gestational age were compared, serum progesterone levels were always significantly lower, while those of progesterone metabolites were higher, in women with AHP. Our results suggest that AHP is a relatively common condition in our geographical location, where ICP is rarely diagnosed. Changes in the serum BA pattern in hypercholanaemia resemble these described in ICP. The simultaneous finding of lower serum total progesterone levels along with an increase in its metabolites supports the hypothesis that a primary defect in progesterone metabolism may be involved in the aetiology of ICP.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1988) 75 (1): 13–20.
Published: 01 July 1988
... bile duct ligated rats, indicating that the severity of cholestasis is almost identical in both models. 2. Plasma alkaline phosphodiesterase I was increased by only 50–80% while alkaline phosphatase was increased more than threefold after ANIT administration. This is in contrast to an earlier study [S...
Abstract
1. Administration of α-naphthylisothiocyanate (ANIT) to rats produced dose-dependent increases in plasma bile acid and bilirubin concentrations. Similar increases in plasma bile acid and bilirubin concentrations were evident in bile duct ligated rats, indicating that the severity of cholestasis is almost identical in both models. 2. Plasma alkaline phosphodiesterase I was increased by only 50–80% while alkaline phosphatase was increased more than threefold after ANIT administration. This is in contrast to an earlier study [S. R. Simpson, K. Rahman & D. Billington (1984) Clinical Science 67, 647–652] where, after bile duct ligation, serum alkaline phosphodiesterase I was elevated sixfold before any increase in alkaline phosphatase activity became apparent. Thus, plasma alkaline phosphodiesterase I does not offer as sensitive a marker of intrahepatic cholestasis (induced by ANIT) as it does of extrahepatic cholestasis (induced by bile duct ligation). 3. Hepatic alkaline phosphodiesterase I was unaffected by ANIT pretreatment while hepatic alkaline phosphatase was increased up to seven times. It is suggested that raised plasma alkaline phosphodiesterase I is due to regurgitation of the biliary enzyme rather than overspill of the enzyme from liver into blood. 4. Gel filtration showed that 24 h and 96 h after ANIT administration, rat serum contained a high molecular weight form of alkaline phosphodiesterase I, suggesting a different isoenzyme profile.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1985) 68 (2): 127–134.
Published: 01 February 1985
...Folkert Kuipers; Rick Havinga; Roel J. Vonk 1. Sulphated glycolithocholic acid (SGLC) causes cholestasis in experimental animals, despite its sulphated form. In the present study, the cholestatic potency and the pharmacokinetics of SGLC were investigated in rats under two conditions: ( a ) in the...
Abstract
1. Sulphated glycolithocholic acid (SGLC) causes cholestasis in experimental animals, despite its sulphated form. In the present study, the cholestatic potency and the pharmacokinetics of SGLC were investigated in rats under two conditions: ( a ) in the presence of an intact circulating bile acid pool and ( b ) after exhaustion of the bile acid pool by 24 h of bile diversion. 2. Intravenous administration of SGLC (8 μmol/ 100 g body weight) to rats with an intact bile acid pool did not cause cholestasis. However, biliary phospholipid and cholesterol concentrations were reduced by 40% and 29% respectively during the first hour after administration. When the same dose of the bile acid was injected in rats with a 24 h biliary drainage, a complete cessation of bile production was observed within 1 h. Twelve hours after the onset of cholestasis, bile production gradually increased again, showed a marked overshoot, and reached control levels after 3 days. In the recovery phase, biliary phospholipid and cholesterol concentrations were greatly reduced. 3. The absence of endogenous bile acids did not change the hepatic clearance rate of a tracer dose of radiolabelled SGLC, but markedly decreased its biliary excretion rate. 4. It was concluded that the hepatotoxic effect of SGLC is much more pronounced in rats with an exhausted bile acid pool, possibly due to a slower biliary excretion of the toxic compound. This phenomenon may have clinical implications for patients with a contracted bile acid pool.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1984) 67 (6): 647–652.
Published: 01 December 1984
... 1984 2 7 1984 © 1984 The Biochemical Society and the Medical Research Society 1984 alkaline phosphodiesterase I cholestasis Clinical Science (1984) 67, 647-652 647 Serum alkaline phosphodiesterase I in experimental biliary obstruction in the rat STUART R . SIMPSON, K . RAHMAN A N D...
Abstract
1. Alkaline phosphodiesterase I was present in rat liver at approx. 100-fold greater activity than alkaline phosphatase, and in rat bile at approx. 25-fold greater activity. 2. Rat serum alkaline phosphodiesterase I was increased 6-fold whilst serum alkaline phosphatase was increased only 2-fold 96 h after bile duct ligation. 3. In contrast to alkaline phosphatase, hepatic alkaline phosphodiesterase I was not affected by bile duct ligation, suggesting its raised serum activity was due to bile regurgitation rather than overspill of the enzyme from liver into blood. 4. Gel filtration showed that 8 and 96 h after bile duct ligation the serum contained a high molecular weight form of alkaline phosphodiesterase I. 5. It is suggested that alkaline phosphodiesterase I offers a potentially useful indicator of biliary obstruction in the rat.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1984) 67 (1): 61–68.
Published: 01 July 1984
... 1983 9 1 1984 © 1984 The Biochemical Society and the Medical Research Society 1984 bile acids biliary tract bilirubin cholestasis external bile drainage Clinical Science (1984) 67,61-68 61 The biliary excretion of sulphated and non-sulphated bile acids and bilirubin in patients...
Abstract
1. The biliary excretion of total bilirubin and bile acids, and the fate of tracer doses of radioactive sulphated and non-sulphated bile acids, were studied in patients with percutaneous transhepatic bile drainage. 2. Non-sulphated bile acids were excreted in bile early after biliary decompression, and the serum total 3α-hydroxy bile acid concentrations fell rapidly to normal. Biliary bilirubin excretion was both less than and delayed compared with that of bile acids, and the serum bilirubin concentration fell more slowly. 3. The serum disappearance of [ 3 H]chenodeoxycholate-3-sulphate was slower than that of [ 14 C]glycocholate in all patients with bile drainage, the difference being more marked in the jaundiced patients. 4. The radioactive sulphated bile acids were recovered predominantly in the urine of the jaundiced patients. In contrast [ 14 C]glycocholate was excreted almost exclusively in bile. In an anicteric patient, radioactive sulphated bile acid disappeared from the serum more quickly, and biliary recovery exceeded that in the urine. 5. The studies demonstrate the differences in handling of total bilirubin, and sulphated and non-sulphated bile acids in man after the relief of bile duct obstruction. The biliary excretion of radioactive labelled sulphated bile acids is low for at least 1 week after biliary drainage, but later becomes the predominant route for excretion in the anicteric patient.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1983) 65 (1): 77–84.
Published: 01 July 1983
.... in contrast, the binding of [ 3 H]glycochenodeoxycholate and [ 3 H]glycochenodeoxycholate-3-sulphate were not altered by the severity of the cholestasis. 4. Studies in vitro indicated that the reduction in the binding of [ 14 C]glycocholate in cholestatic liver disease was not due to high...
Abstract
1. A micro-partition centrifugal ultrafiltration technique has been used to monitor the percentage of[ 14 C]glycocholate,[ 3 H]glycochenodeoxycholate and[ 3 H]glycochenodepxycholate-3-sulphate bound to serum proteins of patients with cholestatic liver disease. 2. in comparison with normal individuals the percentage of binding of [ 14 C]glycocholate and, to a lesser extent, of [ 3 H]glycochenodeoxycholate and [ 3 H]glycochenodeoxycholate-3-sulphate was reduced. 3. The binding of [ 14 C]glycocholate was inversely related to the serum bile salt and bilirubin concentrations. in contrast, the binding of [ 3 H]glycochenodeoxycholate and [ 3 H]glycochenodeoxycholate-3-sulphate were not altered by the severity of the cholestasis. 4. Studies in vitro indicated that the reduction in the binding of [ 14 C]glycocholate in cholestatic liver disease was not due to high concentrations of bile salts, unconjugated bilirubin or fatty acids.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1982) 63 (1): 65–73.
Published: 01 July 1982
... cholestasis gas chromatography—mass spectrometry pruritus Clinical Science (1982) 63,65-73 65 Bile acid profiles of human serum and skin interstitial fluid and their relationship to pruritus studied by gas chromatography-mass spectrometry T . C . B A R T H O L O M E W , J . A . S U M M E R F I E L D , B...
Abstract
1. Pruritus was assessed in 19 patients by measurement of nocturnal limb movement. 2. Serum (nine pruritic, ten non-pruritic) and interstitial fluid (five pruritic, three non-pruritic) bile acids were fractionated according to their mode of conjugation by using DEAP-Sephadex LH-20 and measured by gas chromatography—mass spectrometry. 3. No correlation was found between serum or interstitial fluid total bile acid or individual bile acid concentrations and pruritus. Bile acid profiles in the two groups of patients were similar and there was no correlation between pruritus and the conjugation pattern. 4. The bile acid profile of interstitial fluid reflected that of serum and a linear relationship was found between serum and interstitial fluid bile acid concentrations ( r = 0·95, P < 0·001). 5. The proportion of bile acid sulphate in interstitial fluid was significantly smaller than that in serum ( P < 0·025), where sulphates accounted for up to 46% of the total bile acids. 6. In three patients, a decrease in serum bile acid concentrations achieved by percutaneous transhepatic biliary drainage had little or no effect on pruritus. 7. These findings suggest that bile acids do not have a causative role in the pruritus of cholestatic liver disease.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1981) 61 (6): 773–780.
Published: 01 December 1981
...C. L. Corbett; T. C. Bartholomew; Barbara H. Billing; J. A. Summerfield 1. the apparent renal clearance of intravenously injected [ 14 C]glycocholate and [ 3 H]-chenodeoxycholate-3-sulphate was estimated in 22 patients with cholestasis. the degree of protein binding of the isotopes in serum from...
Abstract
1. the apparent renal clearance of intravenously injected [ 14 C]glycocholate and [ 3 H]-chenodeoxycholate-3-sulphate was estimated in 22 patients with cholestasis. the degree of protein binding of the isotopes in serum from these patients was determined. the effects of pharmacological agents, changes in urine flow rate and pH on renal clearance were studied. 2. the mean renal clearance of [ 14 C]glycocholate was 1.7 ± 0.4 ml/min (mean ± sem), and that of [ 3 H]chenodeoxycholate-3-sulphate was 6.4 ± 0.9 ml/min. [ 14 C]Glycocholate was 80.1% protein bound and [ 3 H]chenodeoxycholate-3-sulphate 96.5% protein bound. 3. Comparisons of the observed clearance rates with those calculated on the basis of glomerular filtration of the unbound fraction suggest that whereas [ 14 C]glycocholate is predominantly reabsorbed by the renal tubules, [ 3 H]chenodeoxycholate-3-sulphate appears in the urine mainly as the result of tubular secretion. 4. Probenecid, ethacrynic acid, frusemide and bendrofluazide decreased the clearance of both bile acids, implying competition for secretion via the proximal tubular organic acid secretory pathway between these compounds and bile acids. 5. Passive non-ionic diffusion does not seem to be an important mechanism in the renal excretion of bile acids as changes in urine flow rate and pH did not influence bile acid clearance. 6. A greater affinity of the proximal tubular organic acid secretory pathway for sulphated than for non-sulphated bile acids may explain the higher observed renal clearance rate of sulphated bile acids.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1979) 57 (6): 499–508.
Published: 01 December 1979
...L. R. Engelking; S. Barnes; C. A. Dasher; D. C. Naftel; B. I. Hirschowitz 1. The serum bile acid disappearances of tracer doses of [24- 14 C]cholic acid and [1- 14 C]-glycocholic acid were studied in eight normal subjects and 11 patients with chronic liver disease (with or without cholestasis) in...
Abstract
1. The serum bile acid disappearances of tracer doses of [24- 14 C]cholic acid and [1- 14 C]-glycocholic acid were studied in eight normal subjects and 11 patients with chronic liver disease (with or without cholestasis) in order to determine the effect of liver disease on hepatic clearances, reflux of conjugated cholic acid and initial distribution volume of each tracer. 2. Total cholic acid clearance was significantly reduced from normal (7·2 ± 0·7 ml min −1 kg −1 , mean ± se) in patients with liver disease (69–88%, group means) as were unconjugated cholic acid (51–68%) and glycocholic acid (66–83%) clearance. 3. Extensive regurgitation of labelled conjugated cholic acid (after unconjugated cholic acid tracer injection) among cholestatic patients accounted for 69 ± 5% of total 14 C remaining in serum at 70 min, thus masking a less-impaired uptake process. 4. The hepatic extraction efficiency for conjugated cholic acid among controls (86 ± 8%) was greater than that for unconjugated cholic acid (60 ± 4%), and was greatly reduced among patients (7–27%, group means). 5. Normal subjects and patients with cirrhosis without cholestasis did not distribute the isotope to extravascular, extrahepatic spaces, in contrast to cholestatic patients with serum bile acid concentration > 149μmol/l. 6. Careful evaluation of serum disappearance of bile acids as well as chromatographic separation of regurgitated metabolites, could provide investigators with indirect evidence of defects in the rate-limiting steps (uptake, conjugation or excretion) of hepatic bile acid transport.
Articles
Journal:
Clinical Science
Clin Sci Mol Med (1977) 52 (6): 585–590.
Published: 01 June 1977
... three enzymes which are often used as alternatives in the assessment of patients with liver disease. 10 9 1976 27 1 1977 © 1977 The Biochemical Society and the Medical Research Society 1977 alkaline phosphatase cholestasis 5′-nucleotidase γ-glutamyl transferase liver...
Abstract
1. The distribution of three membrane-bound enzymes, alkaline phosphatase, 5′-nucleotidase and γ-glutamyl transferase, has been examined in rat liver fractionated into parenchymal cells, a Kupffer cell fraction and a biliary tract fraction by perfusion with collagenase solution. 2. In control rat livers the highest enzyme concentrations were found in Kupffer cell preparations. The fraction enriched with biliary tract cells showed concentrations two- to fourfold those in isolated parenchymal cells. 3. At 24 h after ligation of the bile duct there was a fourfold increase in the alkaline phosphatase activity in parenchymal cells and a 2·5-fold increase of the same enzyme in the biliary tract fraction. The concentration of alkaline phosphatase in Kupffer cells remained unchanged. 4. 5′-Nucleotidase and γ-glutamyl transferase concentrations tended to decrease after bile-duct ligation for 24 h, the most marked changes being found in Kupffer cells. 5. After bile-duct ligation for 7 days the overall activities of hepatic alkaline phosphatase and γ-glutamyl transferase increased fourfold and there was a small rise in 5′-nucleotidase. For alkaline phosphatase and γ-glutamyl transferase the changes were found primarily in parenchymal cells and in the biliary tract fraction. There was a small rise in the activity of 5′-nucleotidase in parenchymal cells and a fall in activity in Kupffer cells. 6. These data show marked differences in the distribution and behaviour of three enzymes which are often used as alternatives in the assessment of patients with liver disease.