H Lafont

Unité Inserm U1077, Caen, Lower Normandy, France

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Publications (206)628.15 Total impact

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    ABSTRACT: The effects of weak external electric fields (1.5–3 V, 30–60 μA) on bile salt secretion by jji situ rat liver were studied after interruption (experiment A) and restoration (experiment B) of the enterohepatic bile salt cycle. In experiment A, bile salt tracer was injected in bolus 3 hr after application of the electric field (14C-TC, 14C-CA, or 14C-DCA). In experiment B, 36 μmoles/h of TC or CA were infused 150 min after application of the electric field until the end of the experiment. A bolus (14C-TC and 14C-CA) was injected 170 min after application of the electric field. The hepatic taurine pool was prelabeled in both experiments. Application of electric fields delayed secretion of 14C-TC into the bile. This delay was longer at 60 μA than at 30 μA Neither field had any effect on 3H-tauroconjugation. Electric fields also led to the formation of osmiophilic globules in hepatocytes and, especially in experiment B, collagen fibers in intracellular spaces. Thus electric fields may provoke changes in plasmic membranes probably in connection with those in the extracellular matrix.
    Electromagnetic Biology and Medicine 07/2009; 7(1):33-55. · 0.81 Impact Factor
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    ABSTRACT: We investigated (a) in vitro and in vivo the changes of biliary mass of the anionic peptide fraction, apolipoproteinA-I, immunoglobulin-A, albumin and cholesterol over time in the excluded gallbladder and (b) in vivo the localization in the gallbladder epithelium of the anionic peptide fraction and cholesterol absorbed from bile. Native bile was substituted with pig bile containing radiolabeled cholesterol in the in vitro isolated intra-arterially perfused pig gallbladder (n=9) and in vivo in anestethized pigs with excluded gallbladders (n=6). The amount of cholesterol (scintillation counting) and proteins (enzyme-linked immunosorbent assay) in gallbladder bile were measured over time. The localization of the anionic peptide fraction and cholesterol absorbed from bile in the gallbladder epithelium was studied in vivo by immunohistochemistry and fluoro-phospho-imager analysis. The rate of biliary cholesterol disappeared from bile was a function of the initial concentration and of the biliary mass changes over time of the anionic peptide fraction, but not of that of the other biliary proteins. The anionic peptide fraction colocalized with biliary cholesterol absorbed by the gallbladder on the apical side of gallbladder epithelial cells. These data indirectly suggest that biliary anionic peptide fraction could favour biliary cholesterol absorption by the gallbladder epithelium.
    Digestive and Liver Disease 08/2007; 39(7):646-53. · 3.16 Impact Factor
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    ABSTRACT: The inhibition of pancreatic lipase activity by extracts of raw, milled or processed cereals was measured in vitro. The inhibitory activity was high in durum wheat, soft wheat and millet, moderate in barley and white sorghum and very low in red sorghum. Milling whole-grain into flours markedly decreased the lipase inhibitory activity in all species. In durum wheat, the germ and the aleurone-layer fraction exhibited the highest inhibitory activity. Processing of soft wheat by bread making, popping, flaking, drum-drying and extrusion-cooking, or durum wheat by making pasta markedly decreased the lipase inhibitory capacity. Extractible proteins were implicated in the inhibition process. These effects also had some nutritional implications.
    Journal of Food Science 08/2006; 57(2):466 - 469. · 1.78 Impact Factor
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    ABSTRACT: Cholesterol constitutes the major component of most gallstones. It was identified and determined in gallstones by thermal analysis technique (DSC and TG-DTA), mainly by the use of the melting temperature (Tonset=145°C and Tmax=149°C) and by DTG peak decomposition (Tmax=364°C). Cholesterol anhydrous (ChA), which showed endothermic polymorphic peak, Tmax=40°C, without mass loss, was differentiated from cholesterol monohydrate (ChH), which showed a broad endothermic peak, Tmax=59°C, attributed to loss of water of crystallization (theoretical 4.45%). Morphological studies of gallstones were performed by optical microscopy and scanning electron microscopy (SEM). The stones consisted of a pigmented core with a variably-sized irregular central cavity, surrounded by a radially arranged deposits of plate-like ChH. The outer part of the stones showed ChA crystal arborescences. X-ray microanalysis gave a typical spectrum rich in C and O, and in some instances the presence of P, which was attributed to the presence of phospholipids. CaCO3 was easily characterized by TG with the use of DTG decomposition peak at 674°C.
    Journal of Thermal Analysis and Calorimetry 10/2005; 82(2):331-338. · 1.98 Impact Factor
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    ABSTRACT: Cholesterol gallstones affect approximately 10-15% of the adult population in North America. Phosphatidylcholine (PC) is considered to be the main cholesterol solubilizer in bile. This study examined the effect of a PC-enriched diet on gallstone incidence in mice susceptible to cholelithiasis. The result obtained showed that the feeding of a lithogenic (LG) diet for 4 weeks or 8 weeks resulted in cholesterol gallstone incidences of 47% and 89%, respectively. These gallstone incidences were either reduced or prevented when the LG diet was enriched with 2% or 6% PC, respectively. The cholesterol saturation index (CSI) was reduced only in mice fed with LG + 6% PC diet as compared with mice fed the LG diet alone. However, in all groups, the CSI was significantly higher than in mice fed Purina chow diet. The biliary anionic polypeptide fraction (APF) was significantly increased in mice fed the LG + 2% PC diet and was reduced in those fed with LG + 6% PC diet. In conclusion, prevention or delay of gallstone formation was not due to a consistent effect on biliary lipid composition, suggesting a direct effect of PC on cholesterol solubilization and/or the effect of an additional nonlipid biliary component such as APF.
    The Journal of Lipid Research 01/2004; 44(12):2297-303. · 4.39 Impact Factor
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    ABSTRACT: Fatty acid bile acid conjugates (FABACs) are a new family of synthetic molecules designed to solubilize biliary cholesterol. They were shown to prevent and dissolve cholesterol gallstones in inbred C57L/J mice fed a lithogenic, high-fat diet (HFD). In these mice, fatty liver was observed in the controls but not in the FABAC-treated ones. The present study was designed to study the effect of FABAC (arachidyl-amido-cholanoic acid) on diet-induced fatty liver in rats, hamsters, and mice. The fatty liver score (on a scale of 0-4 by light microscopy) was 4.0 in control hamsters and 0.3 in the FABAC-fed hamsters (P <.001). In mice it was 1.5 and 0.4, respectively (P <.01). The lipid/protein ratio in the liver was 1.3 +/- 0.44 (mg lipid/mg protein) in control rats and 0.66 +/- 0.04 in the FABAC group (P =.001) after 14 days. In hamsters it was 1.41 +/- 0.27 and 1.11 +/- 0.20, respectively (P =.03), after 21 days. In Imperial Charles River (ICR) mice the ratio was 0.34 +/- 0.10 and 0.17 +/- 0.07 (P =.03), respectively, after 24 days. Liver fat concentration, measured as mg lipid/g liver tissue, decreased similarly by FABAC feeding. The decrease in liver fat affected mainly the triglyceride levels. FABAC-fed animals gained weight similarly to the controls. Triglyceride absorption was unaffected by FABAC supplementation. In conclusion, oral FABAC therapy prevents/reduces the development of fatty liver in animals consuming a HFD.
    Hepatology 09/2003; 38(2):436-42. · 12.00 Impact Factor
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    ABSTRACT: Cholesterol constitutes the major component of most gallstones. It was identified and determined, in gallstones, issued from eleven patients, by thermal analysis: differential scanning calorimetry (DSC), with the use of the melting temperature and enthalpy, thermogravimetry (TG), with the mass loss of water. Anhydrous cholesterol (ChA) was characterized by two endothermic peaks (polymorphic, melting) and cholesterol monohydrate (ChH) by two endothermic peaks (dehydration, melting), too. Cha needle and Chh plate crystals were observed under polarizing light microscopy. The numerous stones obtained from nine patients were cholesterol stones: the ChA was higher 45 and lower 96%. ChH was present in stones of three patients.
    Journal of Thermal Analysis and Calorimetry 01/2003; 71(2):341-351. · 1.98 Impact Factor
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    ABSTRACT: Evidence is now in favor of protein-facilitated mechanisms for the intestinal cholesterol absorption. Here we report that the unesterified cholesterol uptake by rat jejunal brush border membrane vesicles (BBMVs) is efficient, saturable, and protein-mediated. The human apolipoproteins biliary anionic peptide factor (APF) and A-I (apoA-I) up-regulate micellar cholesterol uptake in a dose-dependent manner, but for all tested concentrations (0.1-20 microM), the lipid-free APF was more efficient than apoA-I. This uptake stimulation was suppressed after addition of Pabs directed to the external lipid-binding domain of the CLA-1/SR-BI and reduced by Pabs directed to the external loop of CD36. Thus, CLA-1/SR-BI and to a lesser extent CD36 are involved in the regulation of intestinal cholesterol uptake. APF, the main protein bound to biliary lipids, is likely one of their physiological effectors. As APF is an unesterified cholesterol carrier, it could facilitate the intestinal absorption of biliary cholesterol.
    Biochemical and Biophysical Research Communications 04/2002; 292(2):390-5. · 2.28 Impact Factor
  • Digestive and Liver Disease - DIG LIVER DIS. 01/2001; 33.
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    ABSTRACT: Gallbladder bile from patients with cholesterol or mixed gallstones frequently contains biliary "sludge", a suspension of cholesterol monohydrate crystals and pigment granules embedded in mucin and proteins. The composition of biliary "sludge" and the preferential localization of mucin and proteins could be an indicator for its potential role in gallstone formation. Ultracentrifugation (100000 g/l h) was used to precipitate "sludge" from bile, and the concentration difference of its main components between native bile and ultracentrifuged bile samples was calculated. After purification of the sediment, immunolocalization was performed for the detection of mucin, IgA, albumin, aminopeptidase, and anionic polypeptide fraction using polyclonal and monoclonal antibodies. The amount of sludge in gallbladder bile was 4.26 mg/ml-0.78 (mean+/-SEM) in patients with cholesterol and 2.51 mg/ml+/-0.39 in patients with mixed stones and cholesterol was the main component (48.9+/-4.6% and 44.4+/-7.1%). The sediment appeared as a mixture of vesicular aggregates and pigment particles which were linked by a gel matrix of mucin containing cholesterol crystals. While anionic polypeptide fraction and aminopeptidase were associated to pigments, IgA was uniformly spread in the crystalline parts of "core-like" structures, and albumin, when it was present, appeared as randomly located small spots. Our study demonstrates that the cholesterol content and the distribution pattern of mucin and different proteins is similar in the sediments of biliary "sludge" to that previously shown in cholesterol and mixed gallstones. This suggests that biliary "sludge" represents an early stage of gallstone formation in these patients.
    Journal of Hepatology 10/2000; 33(3):352-60. · 9.86 Impact Factor
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    ABSTRACT: In the present study, we compared the effects of nibbling and gorging on postprandial lipaemia and lipoproteins, hepatic lipid uptake and atheroma deposition. New Zealand White rabbits were fed on a low-fat (LF) control diet or a peanut oil- (10 g/d) and cholesterol- (0.5 g/d) enriched (HF) diet with the fat and cholesterol components given either by nibbling (HF-N) or gorging (HF-G). After 4 and 8 weeks, rabbits were given a test meal, which was either nibbled or taken as a bolus. The LF diet did not noticeably alter postprantial lipid variables. Triacylglycerol levels, 0-35 h lipid responses and plasma accumulation of dietary lipids were significantly higher in the HF-G group than in the HF-N group, despite higher post-heparin plasma lipase activities. Furthermore, as studied on cultured isolated hepatocytes, the higher the rate of supply of triacylglycerol- and cholesterol-rich lipoproteins (TCRL), the lower the rate of lipid uptake and bile salt secretion. Atheroma deposition was significantly increased by gorging the HF diet and was correlated with levels of most postprandial lipid variables. We conclude that gorging v. nibbling a fat and cholesterol-enriched diet exacerbates postprandial lipaemia by reducing the rate of TCRL clearance and favours atheroma deposition.
    British Journal Of Nutrition 06/2000; 83(5):549-59. · 3.30 Impact Factor
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    ABSTRACT: Cholesterol precipitation from supersaturated bile is the earliest and determinant step in the formation of cholesterol gallstones, which is thought to be diet-dependent. Bile composition, appearance and growth of cholesterol crystals were studied in fresh gall-bladder biles from pigs adapted to four different protein-containing diets over 3 weeks: 160 g dietary protein/kg as casein (C16; n 6), or as soyabean-protein concentrate (S16; n 6), or a mixture of both protein sources (casein-soyabean protein, 70:30, w/w) (CS16; n 6), or 320 g of the mixed protein/kg (CS32; n 6). Moreover, all four diets contained 3 g cholesterol/kg and 50 g beta-cyclodextrin/kg as modifiers of bile composition towards cholesterol pro-crystallization. Cholesterol precipitation was most active after the high-protein diet, CS32, and the casein diet, C16, and lowest after the soyabean-protein diet, S16. It was intermediate after the mixed diet, CS16, but still much lower than in the former two groups. These diet-induced variations were suggested to be mediated through modifications in the biliary profile of bile acids, whereas all other biliary constituents studied were essentially unchanged. The fasting level of plasma cholesterol was lowest in both 160 g protein/kg diets containing soyabean protein (S16 and CS16), highest for the high-protein diet CS32, and intermediate for the C16 diet. These results should encourage clinical studies on the effect of soyabean protein, or other vegetable proteins, for primary or recurrence prevention of cholelithiasis at its earliest stage.
    British Journal Of Nutrition 05/2000; 83(4):411-20. · 3.30 Impact Factor
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    ABSTRACT: Radiation exposure results in an inflammatory reaction with acute as well as subacute consequences. Leukocyte infiltration is one of the predominant early histological changes and involves both cytokines and adhesion molecules. Endothelial cells play a key role in this reaction. We have previously shown the increased production of interleukin 6 (IL-6) and IL-8 and the upregulation in intercellular adhesion molecule 1 (ICAM-1) expression by HUVEC following gamma ray exposure. In the present study, we used the cytokines IL-4 and IL-10 to regulate these radiation-induced manifestations. Human umbilical vascular endothelial cells (HUVEC) were treated with IL-4 and IL-10 (50 pg/ml) either before or after 10- Gy irradiation. Three and seven days after irradiation, IL-6 and IL-8 production by HUVEC (either treated or non-treated) was assessed by enzyme-linked immunosorbent assay (ELISA). Our results show that IL-4, when added after irradiation, reversed the radiation-induced increase in IL-8 production, although slightly increased IL-6 production. IL-10 decreased both IL-8 and IL-6 production when added after irradiation. ICAM-1 expression was evaluated 3 days after irradiation by flow cytometry. The radiation-induced upregulation in ICAM-1 expression remained unaffected by the use of IL-4. Altogether, our results show that radiation-induced endothelial cell activation may be ameliorated by IL-4 and/or IL-10, which is of significance in designing strategies for cytokine-mediated intervention and/or therapy of radiation damage.
    Cytokine 12/1999; 11(11):831-8. · 2.52 Impact Factor
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    ABSTRACT: Although several investigations have linked the degree of fatty acid saturation to plasma lipid responses in the postprandial state, further evaluation is necessary. In this study, we compared the effect of saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids on postprandial lipid metabolism using complementary in vivo and in vitro approaches. Fat (10 g) cholesterol (0.5 g) test meals that provided either lard (SFA), olive oil (MUFA), or sunflower oil (PUFA) were ingested by chow-fed New Zealand white rabbits (n = 8). In addition, hepatic uptake of triglyceride-cholesterol-rich lipoproteins (TCRL) isolated from rabbits chronically ingesting SFA, MUFA, or PUFA diets was measured using freshly isolated chow-fed rabbit hepatocytes. Whatever dietary fatty acids ingested, postprandial triglyceridemia and occurrence of radiolabelled dietary lipids in plasma were not markedly different. Conversely, SFA induced higher postprandial cholesterolemia and phospholipemia than MUFA (P < 0.05) whereas PUFA prevented postprandial cholesterol increase. TCRL disappearance from cultured liver cell media was delayed with SFA-rich TCRL and faster with PUFA whereas MUFA-rich TCRL showed an intermediate figure. From these data, we conclude that SFA, MUFA, and PUFA elicited different postprandial plasma and lipoprotein lipid responses. The fatty acid composition of TCRL had a major impact on their subsequent metabolism, especially uptake by cultured hepatocytes. The SFA-induced hypercholesterolemia could be related to an altered hepatic uptake whereas a faster clearance and hepatic uptake could explain the cholesterol-lowering effect of PUFA in rabbits. MUFA, like PUFA, accelerate uptake by hepatocytes but favor cholesterol ester enrichment of TCRL.
    The Journal of Nutritional Biochemistry 08/1999; 10(8):458-66. · 4.55 Impact Factor
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    ABSTRACT: Metabolic and vascular abnormalities are implicated in the pathogenesis of diabetic neuropathy. Two principal metabolic defects are altered lipid metabolism resulting from the impairment of delta-6-desaturase, which converts linoleic acid (LA) into gamma linolenic acid (GLA), and reduced nerve Na+, K+ ATPase activity. This reduction may be caused by a lack of incorporation of (n-6) fatty acids in membrane phospholipids. Because this ubiquitous enzyme maintains the membrane electrical potential and allows repolarization, disturbances in its activity can alter the process of nerve conduction velocity (NCV). We studied the effects of supplementation with GLA (260 mg per day) on NCV, fatty acid phospholipid composition, and Na+, K+ ATPase activity in streptozotocin-diabetic rats. Six groups of 10 rats were studied. Two groups served as controls supplemented with GLA or sunflower oil (GLA free). Two groups with different durations of diabetes were studied: 6 weeks with no supplementation and 12 weeks supplemented with sunflower oil. To test the ability of GLA to prevent or reverse the effects of diabetes, two groups of diabetic rats were supplemented with GLA, one group for 12 weeks and one group for 6 weeks, starting 6 weeks after diabetes induction. Diabetes resulted in a 25% decrease in NCV (P < 0.0001), a 45% decrease in Na+, K+ ATPase activity (P < 0.0001), and an abnormal phospholipid fatty acid composition. GLA restored NCV both in the prevention and reversal studies and partially restored Na+, K+ ATPase activity in the preventive treatment group (P < 0.0001). These effects were accompanied by a modification of phospholipid fatty acid composition in nerve membranes. Overall, the results suggest that membrane fatty acid composition plays a direct role in NCV and confirm the beneficial effect of GLA supplementation in diabetic neuropathy.
    The Journal of Nutritional Biochemistry 07/1999; 10(7):411-20. · 4.55 Impact Factor
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    ABSTRACT: The ability of two 15-ketosubstituted sterols, 5alpha-cholest-8(14)-en-3beta-ol-15-one and 3beta-(2-hydroxyethoxy)-5alpha-cholest-8(14)-en-15-one, to alter the mRNA levels of 3-hydroxy-3-methylglutaryl-CoA reductase, low density lipoprotein receptor, and oxysterol binding protein was studied and compared with the effects of 25-hydroxycholesterol in Hep G2 cells. All three oxysterols decreased the level of HMG CoA reductase mRNA at concentrations of 10-30 microM, although 25-hydroxycholesterol was effective at concentrations of 1-3 microM. 25-Hydroxycholesterol lowered the level of LDL receptor mRNA more efficiently after 8 hours than after 24 hours of incubation, whereas 15-ketosterols did not decrease the mRNA level of the LDL receptor. The transcriptions of HMG CoA reductase and LDL receptor genes are therefore independently regulated by 15-ketosterols in Hep G2 cells. In addition, the level of the oxysterol binding protein mRNA is not affected by oxysterols in Hep G2 cells.
    Biochemical and Biophysical Research Communications 07/1999; 259(3):688-94. · 2.28 Impact Factor
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    ABSTRACT: An overview on the applications and the contributions of electrophoretic techniques to the analysis of biliary proteins is presented. The electrophoretic techniques include free-, paper-, agar-, acetate cellulose film- and starch gel-electrophoresis, immunoelectrophoresis, sodium dodecyl sulfate polyacrylamide gel electrophoresis and high resolution two-dimensional gel electrophoresis. These techniques were applied in the separation and characterization of hepatic bile proteins, gallbladder bile proteins, gallstone proteins, and finally vesicular and micellar proteins. The chief contribution of electrophoresis to research in the field of cholesterol crystal and gallstone formation has been in the characterization of pro- and anti-nucleating proteins.
    Analytica Chimica Acta 03/1999; 383(s 1–2):185–203. · 4.39 Impact Factor
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    ABSTRACT: Liver fatty acid-binding protein (L-FABP) is a small cytoplasmic molecule highly expressed in the liver. Since L-FABP exhibits affinities for several biliary components, its presence in bile was explored by Western blotting and competitive ELISA in various mammalian species. A L-FABP-like immunoreactivity was consistently found in both hepatic and gallbladder bile. A close molecular identity between this 14 kDa biliary protein and the purified L-FABP was assessed by immunological analyses and high performance capillary electrophoresis. Pharmacological induction of hepatic L-FABP biosynthesis led to a similar increase in biliary L-FABP levels showing a close relationships between the cytosolic and biliary contents of this protein. Finally, a correlation between the presence of L-FABP in bile and both bile flow and bile acid release was found. These data suggest an output of L-FABP in bile in normal conditions which might be coupled with the physiological release of biliary components.
    Biochimica et Biophysica Acta 02/1999; 1436(3):593-9. · 4.66 Impact Factor
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    ABSTRACT: Synthetic glucocorticoids, such as dexamethasone, and diets enriched with unsaturated fatty acids have been shown to stimulate hepatic bile salt synthesis. This fact led us to investigate the effects of dexamethasone and linoleic acid supplementation on bile secretion. Cholesterol (Ch) and phospholipid secretions are bile acid dependent. Ch and phospholipid in bile are also highly bound to a small apoprotein, the anionic polypeptide factor (APF). In bile, APF may play a physiological role in stabilizing cholesterol:phospholipid vesicles and might also be important in the regulatory process of bile lipid secretion. In order to study the factors influencing bile secretion, the biliary secretion rates of bile lipids and APF were experimentally modulated in perfused rat liver (PRL) and HepG2 cells. As expected, dexamethasone induced an increase in the biliary secretion rate of bile salts (BS) in the two models (PRL: 34 up to 67 nmol/l/min/g liver; HepG2 cells: 234% vs. 100% in controls). The bile secretion rates for phospholipids (PRL: from 5 down to 1.5 nmol/l/min/g liver; HepG2 cells: 93 vs. 100% in controls) and APF (PRL: from 0.34 down to 0.12 microg/l/min/g liver; cells: 86 vs. 100% in controls) rapidly decreased independently from those of BS. The data from experimental cell models supplemented with linoleic acid indicated a correlation between the BS and APF levels (APF: 71 and 63%; BS: 161 and 197% vs. 100% in controls). The phospholipid level was regulated independently from that of APF and BS and increased (106 and 111% vs. 100% in controls), while Ch remained nevertheless unchanged. Our data showed that dexamethasone induced changes in bile and that linoleic acid clearly impaired the regulation exerted by the dexamethasone on bile lipids.
    Digestion 01/1999; 60(6):515-21. · 1.94 Impact Factor
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    ABSTRACT: We explored the possibility that the biliary protein fraction may support part of the variation in the nucleating activity previously measured in gallbladder biles of pigs. Eighteen gallbladder aspirates freshly obtained from three dietary groups (0, 5, or 10% beta-cyclodextrin) of six pigs were chromatographed to purify their total protein fraction. Proteins were quantified, and analysed through electrophoresis and immunoblotting or enzyme-linked immunosorbent assay for albumin, and five putative effectors of cholesterol crystallisation, mucins, immunoglobulin A, 130 kDa, apolipoprotein A-I, and anionic polypeptide fraction. Each total protein fraction was also assayed for its ability to influence cholesterol precipitation, when added to supersaturated model bile. The current data provided evidence that the cholesterol crystallisation-promoting activity of biliary proteins in model biles increased with the beta-cyclodextrin dietary content. This occurred without any significant change in the total biliary protein content, but was associated with a significant decrease in the concentration of albumin and apolipoprotein A-I, resulting in changes in the overall balance of proteins in bile. Comparison of these results with the crystallisation figures previously obtained from the corresponding native biles led us to conclude that biliary proteins might influence the outcome of the crystallisation process, namely the final crystal concentration at equilibrium, but would not systematically represent a major driving force for determining the velocity of crystal formation in native bile of pigs.
    Biochimica et Biophysica Acta 11/1998; 1394(1):74-84. · 4.66 Impact Factor

Publication Stats

2k Citations
628.15 Total Impact Points

Institutions

  • 1974–2007
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 1983–2000
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1997
    • University of Groningen
      • Department of Pediatrics
      Groningen, Province of Groningen, Netherlands
  • 1995–1997
    • Tel Aviv Sourasky Medical Center
      • Gastroenterology Institute
      Tel Aviv, Tel Aviv, Israel
  • 1993
    • Centre Hospitalier Régional Universitaire de Lille
      Lille, Nord-Pas-de-Calais, France
    • Université de Montréal
      • Department of Nutrition
      Montréal, Quebec, Canada
  • 1989
    • Catholic University of Louvain
      Walloon Region, Belgium
  • 1980
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France