| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Biliary aminopeptidase-N and the cholesterol crystallisation defect in cholelithiasis Nunez, L., L. Amigo, et al. (1995), Gut 37(3): 422-6. Abstract: Several biliary proteins have cholesterol crystallisation promoting activity. One of these glycoproteins is aminopeptidase-N, a canalicular ectoenzyme. This study attempted to localise aminopeptidase-N along the biliary tree, to assess its concentration in a series of 98 patients subjected to abdominal surgery, 40 of them without gall stones, and to correlate its concentration with cholesterol crystal formation time of gall bladder bile. Aminopeptidase-N was isolated from purified native biliary vesicles. A specific polyclonal rabbit anti-aminopeptidase-N antibody was prepared for quantitative immunoblotting and for immunolocalisation. Tissue was obtained from liver biopsy specimens and from gall bladders removed at surgery because of gall stone disease. Aminopeptidase-N was immunolocalised to the apical membranes of hepatocytes and to the apical pole of ductular and gall bladder mucosal cells. The nucleation time of gall bladder bile was mean (SD) 4 (3) days in the gall stone group, compared with 21 (18) days in the control group (p < 0.001). Total absolute biliary protein and aminopeptidase-N concentrations were similar in both the control and gall stone patients. There was a reciprocal significant correlation, however, between the nucleation time and the relative aminopeptidase-N concentration (r = -0.35, p < 0.01) only in the gall stone group of patients. This study shows that this apical transmembrane ectoenzyme with cholesterol crystallisation promoting activity is present along the biliary tree and the hepatocyte. These findings support the concept that high concentrations or qualitative changes of biliary aminopeptidase-N contribute to cholesterol gall stone formation. |
| Biliary anionic peptide fraction and apoA-I regulate intestinal cholesterol uptake Jourdheuil-Rahmani, D., M. Charbonnier, et al. (2002), Biochem Biophys Res Commun 292(2): 390-5. 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. |
| Biliary anionic peptide fraction/calcium binding protein inhibits apolipoprotein A-I-mediated cholesterol efflux from cultured cells van Wijland, M. J., D. R. de Waart, et al. (2001), Biochem Biophys Res Commun 287(1): 1-4. Abstract: The ABC transporter ABCA1 has been implicated to control cholesterol efflux in a variety of cell types including macrophages, fibroblasts, and intestinal epithelial cells. In this study we have investigated whether the 6-kD protein anionic peptide fraction/calcium binding protein (APF/CBP) which has homology to apolipoprotein AI may regulate efflux mediated by lipoproteins. APF/CBP was purified from T-tube bile by ultracentrifugation and preparative reversed phase HPLC. Cholesterol efflux to a variety of acceptors was determined using cultured fibroblasts from controls and patients with Tangiers disease. APF/CBP (0.1 to 2.4 microg/ml) inhibited ApoA-1 (2 microg/ml) mediated cholesterol efflux from normal fibroblasts in a dose dependent manner but had no effect on aspecific efflux to methyl-beta-cyclodextrin or phosphatidylcholine liposomes. In ABCA1 deficient fibroblasts no effect of APF/CBP on efflux was seen. We conclude that APF/CBP specifically interferes with ApoA-I mediated cholesterol trafficking. We hypothesize that competitive binding to ABCA1 may explain the decreased ApoA-I mediated efflux from fibroblasts. |
| Biliary cholesterol and bile acid excretion do not increase in hamsters fed cereal-based diets containing cholesterol Cai, G. and T. P. Carr (1999), Metabolism 48(3): 400-5. Abstract: The major compensatory responses to increased cholesterol consumption are decreased cholesterol synthesis and increased cholesterol excretion through the bile either as free cholesterol or bile acids. The objective of this study was to test the hypothesis that biliary cholesterol excretion is increased in hamsters fed low levels of cholesterol reflecting normal human intake. The hypothesis was based on observations that hamsters generally resist changes in bile acid synthesis when fed large amounts of cholesterol; therefore, increased biliary cholesterol excretion represents a potentially significant pathway for elimination of excess cholesterol in this species. Hamsters were fed modified NIH-07 cereal-based diets containing 0.02%, 0.03%, and 0.05% cholesterol (0.04, 0.06, and 0.10 mg cholesterol/kcal, respectively). The primary response to increasing amounts of dietary cholesterol was downregulation of whole-body cholesterol synthesis, reduced from 3.93+/-0.14 micromol x d(-1) x 100 g(-1) body weight in hamsters fed 0.02% cholesterol to 0.52+/-0.14 micromol x d(-1) x 100 g(-1) in the 0.05% cholesterol group. Biliary cholesterol excretion was also slightly reduced in hamsters fed 0.05% cholesterol, whereas bile acid excretion was not altered by dietary cholesterol. Despite a pronounced downregulation of whole-body cholesterol synthesis, liver and plasma cholesterol concentrations increased in hamsters fed 0.05% cholesterol. The data indicate that increased biliary cholesterol excretion is not a major compensatory route of cholesterol excretion in hamsters consuming cholesterol. Furthermore, cholesterol added to the diet at 0.05% appears to be the approximate threshold at which compensatory mechanisms can prevent increases in liver and plasma cholesterol in male Syrian hamsters. Consequently, this species may be an appropriate animal model for "hyperresponding" individuals in the human population. |
| Biliary cholesterol excretion: a novel mechanism that regulates dietary cholesterol absorption Sehayek, E., J. G. Ono, et al. (1998), Proc Natl Acad Sci U S A 95(17): 10194-9. Abstract: The regulation of dietary cholesterol absorption was examined in C57BL/6 and transgenic mice with liver overexpression of the scavenger receptor BI (SR-BI Tg). In C57BL/6 animals, feeding 0.02 to 1% (wt/wt) dietary cholesterol resulted in a dose-dependent decrease in the percentage of dietary cholesterol absorbed. A plot of total daily mass of dietary cholesterol absorbed versus the percentage by weight of cholesterol in the diet yielded a curve suggesting a saturable process with a Km of 0.4% (wt/wt) and a Vmax of 0.65 mg cholesterol/g body weight per day. Dietary cholesterol suppressed hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity, stimulated cholesterol 7alpha-hydroxylase activity, and enhanced fecal excretion of bile acids, but none of these changes correlated with the percentage of dietary cholesterol absorption. Dietary cholesterol also caused an increase in biliary cholesterol concentration, and in this case the concentration of biliary cholesterol was strongly and inversely correlated with the percentage dietary cholesterol absorption (r = -0.63, P < 0.0001). Biliary cholesterol concentration was also directly correlated with daily cholesterol intake, dietary cholesterol mass absorption, and liver cholesterol ester content. Transgene-induced overexpression of SR-BI resulted in a stimulation of excretion of cholesterol into the bile and suppressed percentage dietary cholesterol absorption. Furthermore, biliary cholesterol levels in SR-BI Tg mice were strongly and inversely correlated with the percentage of dietary cholesterol absorbed (r = -0.99, P < 0.0008). In summary, these results suggest that the excretion of cholesterol into the bile plays an important role in regulating the percentage absorption of dietary cholesterol. |
| Biliary cholesterol hypersecretion in gallstone-susceptible mice is associated with hepatic up-regulation of the high-density lipoprotein receptor SRBI Fuchs, M., B. Ivandic, et al. (2001), Hepatology 33(6): 1451-9. Abstract: Enhanced hepatocellular trafficking of cholesterol to the bile canaliculus and cholesterol hypersecretion appears critical for gallstone formation. Therefore, we studied in more detail the hepatic cholesterol transport pathways in a mouse model of cholesterol gallstone disease. Biliary lipid secretion rates, plasma lipoprotein levels, hepatic expression of lipoprotein receptors, lipid regulatory enzymes, and putative cholesterol transporting proteins were analyzed in gallstone-susceptible C57L/J and gallstone-resistant AKR/J mice, which were fed a lithogenic diet. Biliary cholesterol hypersecretion in C57L mice was associated with decreased plasma high-density lipoprotein (HDL) cholesterol levels and significant hepatic induction of the HDL receptor (SRBI) and cholesteryl ester hydrolase. In response to the lithogenic diet, fatty-acid binding protein of liver (FABPL) was markedly induced in both mouse strains. Caveolin 1 was elevated only in plasma membranes of gallstone-susceptible C57L mice, which also failed to down-regulate cholesterol synthesis. These data suggest a role of the reverse cholesterol transport pathway for genetically determined gallstone susceptibility in the mouse. |
| Biliary cholesterol secretion and bile acid formation in the hamster: the role of newly synthesized cholesterol Scheibner, J., M. Fuchs, et al. (1994), J Lipid Res 35(4): 690-7. Abstract: In order to define the source of cholesterol for bile acid synthesis and biliary cholesterol, hamsters with an extracorporeal bile duct received an intraperitoneal bolus of 3Hwater labeling newly synthesized cholesterol. Thereafter the enterohepatic circulation was interrupted and a nutrient solution was infused during the experimental period of 78 h. In a separate group, pravastatin was administered (54-78 h) to allow discrimination of 3H-labeled cholesterol recycling from plasma and newly synthesized hepatic cholesterol late during the experiment. In controls, newly synthesized biliary cholesterol and primary bile acids derived from cholesterol newly synthesized during the experiment amounted to 5% and 12% immediately after depletion of the bile acid pool (6-9 h), respectively. After longterm bile diversion these proportions increased to 56-63%, whereas 71% of plasma cholesterol was labeled. Pravastatin inhibited the secretion of biliary cholesterol, cholate, and chenodeoxycholate by 30, 50, and 44%, respectively. In contrast, the preinfusion tritium label was suppressed by a maximum of 16%, 14%, and 26%, respectively, reflecting the contribution of cholesterol newly synthesized in the hepatocyte as opposed to labeled cholesterol recycling from the plasma. It is concluded that in the hamster newly synthesized cholesterol is of minor importance as substrate for bile acid synthesis as well as biliary cholesterol, both under near physiologic conditions and after long-term bile diversion. Moreover, the hepatic cholesterol pools subserving the synthesis of the primary bile acids are identical but appear to be different from that of biliary cholesterol directly after the depletion of the enterohepatic bile acids. |
| Biliary cholesterol secretion by the twinned sterol half-transporters ABCG5 and ABCG8 Wittenburg, H. and M. C. Carey (2002), J Clin Invest 110(5): 605-9. |
| Biliary cholesterol secretion: more lessons from plants? Stieger, B. (2003), J Hepatol 38(6): 843-6. |
| Biliary cholesterol transport and precipitation: introduction and overview of conference Strasberg, S. M. and P. R. Harvey (1990), Hepatology 12(3 Pt 2): 1S-5S. Abstract: Cholesterol is secreted into bile as cholesterol-phospholipid vesicles. The cholesterol and phospholipid are subsequently exposed to the bile salts contained in the bile, which leads to the process of micellation. Two situations may arise depending on whether there is enough bile salt in proportion to cholesterol to complete this "maturation" process. If the cholesterol saturation is low, at equilibrium the bile salts will have completely micellized the vesicles. On the other hand, if bile is saturated with cholesterol, the micellation process is incomplete and vesicles and micelles will be present at equilibrium. The residual vesicle in this latter situation may have a higher cholesterol/phospholipid ratio because of the greater propensity of phospholipid to be micellized. This situation may result in cholesterol nucleation. The mechanism of nucleation from vesicles and the possible role of nucleating and antinucleating proteins in this process have been discussed. |
| Biliary cholesterol transport and the nucleation defect in cholesterol gallstone formation O'Leary, D. P. (1995), J Hepatol 22(2): 239-46. |
| Biliary excretion of chylomicron remnant cholesterol in the rat: responses to the expansion of their plasma pool and promoting role of stimulated bile-acid synthesis Carrella, M., A. Csillaghy, et al. (1995), Clin Sci (Lond) 89(2): 121-8. Abstract: 1. Chylomicron remnants, the intermediate intestinal lipoproteins carrying the bulk of dietary cholesterol, are actively taken up and degraded in the hepatocytes, releasing cholesterol which can be excreted in bile. To study this pathway, a mass of remnants, leading to a consistent rise in hepatic cholesterol, was administered as an intravenous bolus in rats with chronic bile fistula equilibrated by water, electrolyte and taurocholate infusions, and changes in biliary lipids and bile acids were evaluated for up to 24 h in comparison with baseline. 2. A mean 16% increase in the net output of bile acids was observed at each time interval after lipoprotein injection, accounting for a 24h cumulative excretion of approximately one-third of the administered cholesterol mass. These changes did not reach statistical significance however. The cholesterol output and concentrations of all biliary lipids did not vary either. Without taurocholate replacement, remnants injection was followed by a 15-20% decrease in bile acid and bile lipid secretion, presumably due to an insufficient hepatic bile-acid flux. 3. When 3Hcholesterol-labelled remnants were administered at the same mass in the chronic equilibrated bile fistula model, 21% of injected radioactivity was excreted in 24h, distributing mostly in acidic rather than neutral sterols (20.02 +/- 1.85 compared with 1.07 +/- 0.04), with an acidic to neutral sterol mean ratio of 16. 4. To exclude interfering effects from the administered cholesterol mass and chronic bile fistula, 3H-labelled remnants were also studied as a cholesterol trace injected in rats with acute bile fistula.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Biliary haptoglobin, a potent promoter of cholesterol crystallization at physiological concentrations Yamashita, G., S. Ginanni Corradini, et al. (1995), J Lipid Res 36(6): 1325-33. Abstract: BACKGROUND/AIMS: Several proteins present in human bile have been reported to promote cholesterol crystallization and thus are potentially important in the formation of cholesterol crystals as the initial stage in gallstone pathogenesis. To be physiologically relevant, such proteins must either be present in high concentration in bile or have a potent promoting activity. The current study explored several of the more abundant but unexamined biliary proteins based upon their also having sufficiently high serum concentrations that antibodies were available for both their isolation and quantitation. METHODS: Protein purification was accomplished by immunoaffinity chromatography of bile followed by delipidation. Con A affinity chromatography of bile was used to obtain the bound fraction, a portion of which was delipidated. Crystallization-promoting activity of both the purified proteins and Con A-bound glycoprotein fractions (CABG) was measured by a photometric crystal growth assay. A competitive antibody-capture ELISA assay was developed to measure concentrations of alpha 1-antitrypsin, transferrin, and haptoglobin in native bile. RESULTS: At their relevant physiological concentrations, biliary haptoglobin (15 micrograms/ml) had a crystallization-promoting activity twice that of the biliary IgM (75 micrograms/ml) used as a reference standard (P < 0.05). Biliary transferrin (20 micrograms/ml) had only modest promoting activity (P < 0.05). Biliary alpha 1-antitrypsin (50 micrograms/ml), by contrast, showed no promoting activity. Delipidation of the CABG fraction decreased its promoting activity by 75%. Biliary haptoglobin accounts for about 30% of delipidated total CABG-promoting activity. CONCLUSIONS: Biliary haptoglobin at its physiological concentration has a highly potent crystallization-promoting activity and thus becomes a candidate for major attention in understanding gallstone pathogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Biliary lipid composition and metastability of biliary cholesterol in patients with acalculous cholesterolosis Chijiiwa, K., K. Nakano, et al. (1992), Clin Chim Acta 212(1-2): 65-71. |
| Biliary lipid composition in cholesterol microlithiasis Fracchia, M., S. Pellegrino, et al. (2001), Gut 48(5): 702-6. Abstract: BACKGROUND: Little information is available on the pathogenesis of cholesterol microlithiasis, and it is not clear if biliary lipid composition in these patients is similar to changes seen in cholesterol gall stone patients. AIMS: To measure biliary lipid composition in patients with cholesterol microlithiasis. PATIENTS: Eleven patients with cholesterol microlithiasis, 20 cholesterol gall stone patients, and 17 healthy controls. METHODS: Duodenal bile was collected in the fasting state during ceruletide infusion. Biliary cholesterol, phospholipids, and total bile acids were analysed by enzymatic assays, and conjugated bile acids by high pressure liquid chromatography. RESULTS: Patients with microlithiasis had a cholesterol saturation index significantly higher than controls (mean value 1.30 (95% confidence interval 1.05-1.54) v 0.90 (0.72-1.08)) but similar to gall stone patients (1.51 (1.40-1.63)). This was due to a significant decrease in per cent phospholipid (10.0% (7.1-12.8)) compared with controls (21.4% (18.1-24.6)) and gall stone patients (24.9% (20.5-29.3)). Per cent cholesterol was similar in patients with microlithiasis and controls (5.3% (4.5-6.1) and 5.6 % (4.3-6.8), respectively) but was significantly increased in gall stone patients (10.9% (9.3-12.4)). Bile acid composition in patients with microlithiasis was similar to controls whereas in gall stone patients deoxycholic acid was significantly increased: 27.3% (24.8-29.7) v 19.0% (15.7-22.2) in controls and 20.6% (14.9-26.2) in patients with microlithiasis. CONCLUSION: Patients with cholesterol microlithiasis have biliary cholesterol supersaturation, similarly to cholesterol gall stone patients. Whereas in the latter this is due to increased per cent cholesterol, in patients with microlithiasis this is caused by phospholipid deficiency, with normal per cent cholesterol and normal biliary bile acid composition. |
| Biliary lipid composition in patients with cholesterol and pigment gallstones and gallstone-free subjects: deoxycholic acid does not contribute to formation of cholesterol gallstones Gustafsson, U., S. Sahlin, et al. (2000), Eur J Clin Invest 30(12): 1099-106. Abstract: BACKGROUND: Four main disturbances have been attributed to cholesterol gallstone disease: hypersecretion of cholesterol from the liver with cholesterol supersaturation in bile; disturbed motility with defective absorption and secretion by the gallbladder; increased crystallisation of cholesterol in the gallbladder bile; and slow intestinal transit with increased amount of deoxycholic acid in the bile acid pool. We aimed to evaluate the biliary lipid composition in a large series of gallstone patients, with emphasis on the amount of deoxycholic acid and with respect to number of stones, compared to gallstone free subjects. MATERIALS AND METHODS: Bile was sampled during operations through puncture of the gallbladder from 145 cholesterol gallstone patients, 23 patients with pigment stones and 87 gallstone free patients undergoing cholecystectomy. Biliary lipid composition, cholesterol saturation, bile acid composition, nucleation time and cholesterol crystals were analysed. RESULTS: The patients with cholesterol gallstones showed higher molar percentage of cholesterol, lower total biliary lipid concentration, higher cholesterol saturation, shorter nucleation time and higher proportion of crystals in bile than the other groups. The nucleation time was significantly shorter in multiple cholesterol gallstone patients, but this was not due to higher cholesterol saturation. Male cholesterol gallstone patients showed higher cholesterol levels, lower total biliary lipid concentration, and higher cholesterol saturation in bile than female patients. There was no difference in biliary content of deoxycholic acid, but significantly lower content of cholic acid in gallstone patients compared to gallstone free patients. CONCLUSIONS: We conclude that deoxycholic acid does not contribute to gallstone formation in cholesterol gallstone patients. The short nucleation time in patients with multiple cholesterol stones is not due to higher cholesterol saturation. |
| Biliary lipid secretion: immunolocalization and identification of a protein associated with lamellar cholesterol carriers in supersaturated rat and human bile Rigotti, A., L. Nunez, et al. (1993), J Lipid Res 34(11): 1883-94. Abstract: Feeding a 0.5% diosgenin plus 0.02% simvastatin diet to rats increases biliary cholesterol concentration and saturation to levels generally found in human native supersaturated bile. By using preparative ultracentrifugation, gel filtration chromatography, and electron microscopy, we isolated, purified, and identified lamellar structures (unilamellar vesicles and multilamellae) as a major biliary cholesterol transport in supersaturated human and rat bile. It was estimated that more than 60% of biliary cholesterol is transported in these lamellar carriers, which were identified by transmission electron microscopy as unilamellar vesicles and multilamellar bodies within bile canaliculi of rats with cholesterol supersaturated bile. By SDS-PAGE, a characteristic and constant protein profile was found associated to the purified lamellar carriers. One of these proteins, a 130-kDa protein, was isolated from human biliary lamellae and used for preparation of a rabbit polyclonal antibody, which cross-reacted with the homologous rat protein. By Western blotting, it was established that the purified low density fraction of bile-Metrizamide gradients, containing lamellae, was enriched with the 130-kDa protein. The 130-kDa protein was characteristically detected at the canalicular membrane by Western blotting of hepatic subcellular fractions and by immunohistochemistry of rat and human liver biopsies. Amino acid sequencing of the amino terminus of the 130-kDa protein demonstrated a complete identity with aminopeptidase N, a canalicular transmembrane hydrophobic glycoprotein. These studies show that biliary lipids may acquire an ordered multilamellar structure that is present in the canaliculi of rats with supersaturated bile. These biliary lamellae are similar to lamellar bodies and surfactant-like material frequently found in other epithelia, suggesting common biogenetic, structural, and functional properties. The identification of aminopeptidase N associated with biliary lamellae is consistent with the involvement of the canalicular membrane in the secretory mechanism of biliary lipids. |
| Biliary phospholipases in the prairie dog model for cholesterol cholelithiasis Booker, M. L. and W. W. LaMorte (1994), Hepatology 19(3): 743-9. Abstract: Lysolecithin has been implicated as a contributing factor in the pathogenesis of cholecystitis and cholesterol cholelithiasis. The phospholipases are key enzymes in the generation of a number of metabolites including lysolecithin, but conflicting reports exist concerning the presence of these enzymes in the biliary tract. In this study, measurement of phosphatidylcholine-specific phospholipase activity by means of the hydrolysis of radiolabeled phosphatidylcholine (100 nmol) by 90 micrograms of homogenate protein during a 60-min incubation demonstrated substantial enzyme activities in gastric fundus and distal ileum (90% and 70% hydrolysis, respectively), whereas activity was virtually undetectable in gallbladder mucosa (0.7% hydrolysis). Additional studies were conducted in prairie dogs fed diets high in cholesterol or with trace amounts of cholesterol using homogenates of gallbladder mucosa, seromuscularis and full-thickness tissue, as well as samples of hepatic and gallbladder bile. The only hydrolytic activity in excess of blank values that was detected was a highly variable phospholipase A2 activity in several gallbladder biles from animals given diets with both low levels and high levels of cholesterol, with the enzyme activities of the two dietary groups being similar. These results demonstrate that prairie dog gallbladder contains extremely low levels of phospholipase activity, in marked contrast to other gastrointestinal tissues. However, there was evidence of a phospholipase A2 activity in gallbladder bile. In light of the low activity in gallbladder tissue, the source of this enzyme appears to be the liver and not the gallbladder.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Biliary pronucleating proteins and apolipoprotein E in cholesterol and pigment stone patients van Erpecum, K. J., P. Portincasa, et al. (2003), J Hepatol 39(1): 7-11. Abstract: BACKGROUND/AIMS: Although cholesterol gallstone patients exhibit higher biliary cholesterol saturation than pigment stone patients, underlying mechanisms that affect stone type are unknown. We hypothesized that pronucleating proteins, hydrophobic bile salts or apolipoprotein E genotype affect stone type. We therefore compared these putative factors in cholesterol and pigment stone patients.METHODS: In 74 cholesterol and 12 pigment stone patients, bile lipids, various pronucleating proteins, crystallization and apolipoprotein E genotype were determined.RESULTS: Crystallization was enhanced, and cholesterol saturation higher in case of cholesterol stones, without any difference in bile salt composition. Concentrations of mucin (0.91+/-0.08 versus 0.31+/-0.06 mg/ml: P<0.0001), protein, IgM, IgG, IgA, haptoglobin, alpha1-acid glycoprotein and haptoglobin were 2-6-fold higher in cholesterol stone patients. Twenty cholesterol stone pts (27%) but only one pigment stone pt (8%) had at least one epsilon4 allele. There was a significant difference in allele frequencies between both groups (cholesterol stones similar to Dutch population: epsilon2 0.074, epsilon3 0.770, epsilon4 0.156: pigment stones: epsilon2 0.250, epsilon3 0.708, epsilon4 0.042).CONCLUSIONS: Various pronucleating biliary proteins are markedly higher in cholesterol than pigment stone patients. Also, apolipoprotein E genotype differs between cholesterol and pigment stone patients. These factors may affect gallstone type. |
| Biliary proteins from hepatic bile of rats fed curcumin or capsaicin inhibit cholesterol crystal nucleation in supersaturated model bile Hussain, M. S. and N. Chandrasekhara (1994), Indian J Biochem Biophys 31(5): 407-12. Abstract: Following our earlier observations that curcumin and capsaicin are antilithogenic in mice and hamsters, attempts were now made to understand the manner in which these spice principles were acting. For this purpose, the hepatic biles of rats fed a control, lithogenic, and lithogenic diet supplemented with curcumin or capsaicin were subjected to gel filtration chromatography (sepharose-4B-Cl) and the LMW protein fractions were tested for their ability to influence cholesterol crystal growth in model bile. The LMW protein fraction from the lithogenic group bile shortened the nucleation time and increased the crystal growth rate and final crystal concentration. But with the LMW protein fractions from the biles of rats on the lithogenic group supplemented with curcumin or capsaicin, the nucleation times were prolonged and the crystal growth rates and final crystal concentrations were decreased. The LMW fractions were further purified into three different sugar specific proteins by affinity chromatography. A higher proportion of LMW proteins from the lithogenic group bile was bound to Con-A whereas higher proportions of LMW proteins from the groups fed with curcumin and capsaicin were respectively bound to wheat germ agglutinin and Helix pomatia lectin. The Con-A bound fraction obtained from the lithogenic group showed a pro-nucleating effect. In contrast, the WGA-bound fraction obtained from curcumin group or the Helix pomatia lectin bound fraction obtained from capsaicin group showed a potent antinucleating activity. |