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Susumu Tazuma

Publications and source records attributed to Susumu Tazuma.

At least 37 records · Page 2Linked to original sources
PubMed2005

A nuclear receptor-mediated choleretic action of fibrates is associated with enhanced canalicular membrane fluidity and transporter activity mediating bile acid-independent bile secretion.

Fibrates are commonly used lipid-lowering agents that act via PPARalpha, a member of the nuclear hormone receptor superfamily. The mechanism(s) of fibrate-induced changes in the hepatic canalicular membrane and bile lipids are still unknown. Therefore, the aim of this study was to investigate the influence of fibrates on hepatic lipid metabolism and to assess the hepatocellular cytoprotective effect on hepatocyte canalicular membrane. Male ICR mice were fed standard chow with or without bezafibrate (100 mg/kg) for 6 days. The expression of canalicular membrane transporters (Mdr2 and Mrp2) was evaluated by RT-PCR and Western blotting. Canalicular membrane fluidity was also investigated. Canalicular membrane fluidity was markedly increased by fibrates. The expression of mdr 2 and mrp2 mRNA and protein showed a significant increase in fibrate-treated mice. These results suggested that fibrates improve liver function by enhancing bile secretion. The mechanism of the choleretic action of fibrate therapy might involve the enhancement of bile acid-independent bile secretion, since increased expression of Mdr2 and Mrp2 was found in fibrate-treated animals. These changes were very likely mediated by PPARalpha, and the increase of canalicular membrane fluidity may have been partly associated with enhancement of this transporter activity.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2005

Treatment of pancreatic stones with extracorporeal shock wave lithotripsy: results of a multicenter survey.

OBJECTIVES: A retrospective multicenter survey was performed to evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) as a treatment of pancreatic stones. METHODS: A survey was sent to 11 institutions belonging to the Japanese Association of Extracorporeal Shock Wave Lithotripsy in Digestive Diseases, and data were collected on 555 patients who underwent ESWL for pancreatic stones between January 1990 and September 2002. The male:female ratio was 5.2:1, and the mean age was 52.5 years. The etiology was alcohol related in 425 patients (76.6%) and idiopathic in 111 patients (20.0%); 204 patients (36.8%) had a single stone and 470 patients (84.7%) were symptomatic. RESULTS: Mean frequency of the procedure was 5.0 times (range, 1-29). Fragmentation of stones was achieved in 513 patients (92.4%), and the complete stone clearance rate after ESWL alone or in combination with interventional endoscopy was 72.6%. Symptom relief was achieved in 428 (91.1%) of 470 patients. Thirty-five patients (6.3%) developed complications, including 30 patients (5.4%) who developed acute pancreatitis. Five hundred four (90.8%) patients were followed for a mean of 44.3 months, during which 122 (22.0%) suffered stone recurrence (mean time to recurrence, 25.1 months). Twenty-two (4.1%) of the 504 patients who were followed required surgery. Pancreatic exocrine function improved in 65 patients (38.0%), was unchanged in 49 patients (28.7%), and progressed in 57 patients (33.3%). Pancreatic endocrine function improved in 44 patients (24.3%), was unchanged in 85 patients (47.0%), and progressed in 52 patients (28.7%). CONCLUSION: ESWL is the treatment of choice for clearing pancreatic stones.

Adolescent↗
PubMed2004

Administration of phosphatidylcholine-cholesterol liposomes partially reconstitutes fat absorption in chronically bile-diverted rats.

BACKGROUND AND AIMS: Intestinal bile deficiency in cholestatic patients leads to fat malabsorption. We addressed the potency of model bile, bile salts and phosphatidylcholine (PC)-cholesterol (CH) liposomes to reconstitute fat absorption in permanently bile-diverted (BD) rats. METHODS: The plasma appearance of 13C-labeled palmitic acid (13C-16:0) and linoleic acid (13C-18:2) was determined after their enteral administration to BD or to control rats with an intact enterohepatic circulation (EHC) (13C-16:0 and 13C-18:2 dissolved in 25% olive oil-75% medium chain triacylglycerol oil mixture). BD rats were intraduodenally infused with buffer, model bile [consisting of 60 mM taurocholate (TC), 8 mM PC and 1 mM CH], buffer with TC, buffer with PC and CH liposomes, or buffer with lyso-PC and CH. RESULTS: Plasma concentrations of 13C-16:0 and 13C-18:2 were consistently three- to eightfold higher in control rats than those in buffer-infused BD rats (P < 0.01). ID administration of either model bile or TC to BD rats restored plasma appearance of 13C-fatty acids at least to concentrations observed in control rats. Administration of PC + CH liposomes to BD rats partially reconstituted the plasma appearance of 13C-16:0, but did not affect that of 13C-18:2. Compared with control rats, the area under the curve (AUC) of plasma 13C-16:0 concentrations was 13.0 +/- 6.9% in buffer-infused rats and 40.9 +/- 3.1% in liposome-infused rats (P < 0.005). CONCLUSIONS: Enteral administration of PC + CH liposomes to BD rats partially corrects the absorption of palmitic acid. Present data suggest that administration of PC + CH liposomes could enhance fat absorption in clinical conditions of cholestasis in which bile salt supplemention is contraindicated.

Animals↗
PubMed2004

Identification of rare polymerase variants of hepatitis B virus using a two-stage PCR with peptide nucleic acid clamping.

Emergence of lamivudine-resistant variants, with amino acid substitutions in the Tyr-Met-Asp-Asp (YMDD) motif of hepatitis B virus (HBV) reverse transcriptase, is a serious problem in antiviral therapy. Presence of YMDD motif variants in patients who had never been treated with lamivudine has been reported recently. However, no analysis of nucleotide and amino acid sequences of these variants has been performed. In the present study, using polymerase chain reaction (PCR) with peptide nucleic acid (PNA) clamping, we detected many new variants, such as Tyr-Arg-Asp-Asp (YRDD), Tyr-Met-Asp-Asn (YMDN). Many of them had stop codon(s) in overlapping HBs gene. Although the biological activity of these HBV polymerase variants remains to be determined, our results showed that numerous quasispecies are created during virus replication. A typical lamivudine-resistant Tyr-Val-Asp-Asp (YVDD) variant was detected in only one of 62 (1.6%) anti-HBe patients with HBV infection before administration of lamivudine. This variant did not have the L528M mutation, which is often associated with YVDD variants, and lamivudine therapy in this patient suppressed HBV replication. Thus, care should be taken when interpreting the results of detection of YMDD variants, especially when the sensitivity of the assay is very high. Amplification of rare variants by PCR with PNA seems a useful tool to examine the emergence of drug-resistant variants as well as naturally occurring mutants, such as the hepatitis B e antigen (HBeAg) stop codon and vaccine escape mutants. Examination of rare variants should enhance the understanding of the mechanism for emergence of drug-resistant HBV variants and help in developing strategies for new antiviral drugs.

Adult↗
PubMed2004

Partial characterization of cytoprotective mechanisms of lecithin against bile salt-induced bile duct damage.

BACKGROUND: We recently demonstrated that cyclosporine A causes a disproportionate reduction of biliary lipid secretion, and this is inhibited by hydrophilic bile salts through the enhancing of biliary lecithin secretion. In the present study, the underlying mechanism of such a cytoprotective action of hydrophilic bile salts was determined with attention to the possible role of lecithin. METHODS: Immortalized mouse cholangiocytes were cultured for 4 h with taurine conjugates of a hydrophobic bile salt (cholate [TC]), and hydrophilic bile salts (ursodeoxycholate [TUDC], betamuricholate [TbetaMC], and alphamuricholate [TalphaMC]), at 200 microM, in the presence or absence of lecithin (5, 10, 25, 50, 100, or 200 microM), followed by flow cytometric detection of apoptosis, using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. Cholangiocyte bile salt transporter mRNAs (apical sodium-dependent bile-salt transporter [Asbt] and multidrug resistance protein 3 [Mrp3]) were determined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Apoptosis was induced by all of the bile salts (TC > TUDC, TbetaMC, and TalphaMC). Interestingly, bile salt-induced apoptosis was inhibited by lecithin in a concentration-dependent manner. Further, RT-PCR showed that the expressions of Asbt and Mrp3 mRNAs were enhanced by all the bile salts, whereas lecithin reduced Asbt expression, but enhanced Mrp3 expression. CONCLUSIONS: These findings indicate that bile salts cause bile-duct cell damage through Asbt-mediated uptake, but that biliary lecithin physiologically inhibits such damage by reducing the expression of this transporter. In addition, the induction of Mrp3 expression by lecithin may play a role in inhibiting the accumulation of bile. Thus, the modulation of lecithin secretion into bile may be another important target for the treatment of biliary disorders.

Animals↗
PubMed2004

Gastric acid normosecretion is not essential in the pathogenesis of mild erosive gastroesophageal reflux disease in relation to Helicobacter pylori status.

In the pathogenesis of gastroesophageal reflux disease (GERD), gastric acid is considered to be one of the most important factors, but little is known about the degree of gastric acid secretion in GERD patients. In this study, we evaluated it in GERD patients and control subjects by 24-h intragastric pH, and serological and histological investigations, in relation to Helicobacter pylori (H. pylori) status. In H. pylori-negative GERD patients gastric acid secretion was similar to that in H. pylori-negative control subjects. In H. pylori-positive GERD patients, in particular, mild GERD patients, it decreased significantly compared to that in H. pylori-negative control subjects, but the degree of decrease was smaller than in H. pylori-positive control subjects. Results of serological and histological evaluation were supportive. In conclusion, in some GERD patients, gastric acid secretion was significantly decreased. Increased or maintained gastric acid secretion was not essential in the pathogenesis of mild GERD.

Adult↗
PubMed2004

Immune response in mouse experimental cholangitis associated with colitis induced by dextran sulfate sodium.

BACKGROUND AND AIM: Primary sclerosing cholangitis is frequently complicated by inflammatory bowel disease. Although many colitis models have been reported, little information has been obtained about complicated cholangitis. The aim of the present study was to determine whether hepatobiliary disorders occur in mice experimental colitis, and to clarify the underlying mechanisms. METHODS: The CD-1 mice were fed standard chow with or without dextran sulfate sodium in the drinking water, followed by histological examination of the liver and colon. Mononuclear cells were isolated from these organs, and cytokine production was assessed. The CD4/CD8 ratio and the population of natural killer T (NKT) cells were analyzed by flow cytometry. RESULTS: Inflammatory cell infiltration and focal necrosis in the liver were found in 33% of treated mice. In treated mice, the CD4/CD8 ratio increased in the liver, whereas no such change was found in the colon. Also an increase of interferon-gamma and a decrease of interleukin-4 production were observed. The NKT cell population showed transient changes in the liver and colon. CONCLUSIONS: Hepatobiliary disorders were complicated with experimental colitis in CD-1 mice. Immunological findings indicate a T-helper-1-dominant underlying mechanism, and NKT cells may play a pathogenic role in this model. This model may help to elucidate the relationship between hepatic and colonic inflammations.

Animals↗
PubMed2003

AT1A-deficient mice show less severe progression of liver fibrosis induced by CCl(4).

The renin-angiotensin system has been shown to contribute to fibrogenesis in varieties of organs, including the liver. Here, we investigated whether the angiotensin II type 1A receptor (AT1A) is implicated in the development of liver fibrosis, using AT1A-deficient and wild-type (WT) mice. After single dose of carbon tetrachloride (CCl(4)), there were no significant differences between two groups with regard to hepatic inflammation and necrosis. After 4 weeks of treatment with CCl(4), histological examination revealed that AT1A-deficient mice showed less infiltration of inflammatory cells and less severe progression of liver fibrosis compared with WT mice. These findings were accompanied by the hepatic content of hydoxyproline and the expression of alpha-smooth muscle actin (alpha SMA). The level of transforming growth factor-beta 1 (TGF-beta 1) messenger RNA was markedly higher in WT mice when compared with AT1A-deficient mice. These results confirm that signaling via AT1A plays a pivotal role in hepatic fibrogenesis.

Animals↗
PubMed2003

Inhibition of cholesterol crystallization under bilirubin deconjugation: partial characterization of mechanisms whereby infected bile accelerates pigment stone formation.

Pigment gallstones have been reported to be closely associated with biliary tract infection. We previously reported that addition of unconjugated bilirubin (UCB), which is deconjugated by beta-glucuronidase in infected bile, could enhance cholesterol crystal formation in supersaturated model bile (MB). The present study evaluated the effect of beta-glucuronidase on the processes of pigment gallstone formation and cholesterol crystallization. Supersaturated MB (taurocholate/lecithin/cholesterol at 71:18:11, a total lipid concentration of 10.0 g/dl and a cholesterol saturation index (CSI) of 2.0) and native rat bile were mixed at a ratio of 3:1. Then, mixed bile was incubated with or without beta-glucuronidase and changes of the following parameters were investigated over time: (1) the UCB/total bilirubin ratio; (2) cholesterol crystal formation; (3) the precipitate weight and the cholesterol concentration in the precipitate and supernatant; and (4) the lipid distribution of vesicles in the supernatant. Compared with beta-glucuronidase-free bile, (1) beta-glucuronidase-containing bile showed a significant increase of the UCB/total bilirubin ratio, (2) as well as a significantly longer nucleation time (96+/-17.0 vs. 114+/-20.0) and fewer cholesterol crystals. (3) The precipitate weight and the cholesterol concentration in the precipitate were significantly increased, while the cholesterol concentration in supernatant was decreased. (4) When mixed bile was incubated with beta-glucuronidase, the cholesterol concentration in the vesicles was lower than in bile without beta-glucuronidase. The precipitate weight and the cholesterol concentration in the precipitate was increased by incubation with beta-glucuronidase, while cholesterol concentration was decreased in the supernatant (especially in the vesicles). This means that bile vesicles were more stable and it was more difficult for cholesterol crystals to form. Thus, the presence of beta-glucuronidase may inhibit the formation of pure cholesterol stones even in the presence of cholesterol supersaturation.

Animals↗
PubMed2003

Feeding natural hydrophilic bile acids inhibits intestinal cholesterol absorption: studies in the gallstone-susceptible mouse.

We explored the influence of the hydrophilic-hydrophobic balance of a series of natural bile acids on cholesterol absorption in the mouse. Male C57L/J mice were fed standard chow or chow supplemented with 0.5% cholic; chenodeoxycholic; deoxycholic; dehydrocholic; hyocholic; hyodeoxycholic; alpha-, beta-, or omega-muricholic; ursocholic; or ursodeoxycholic acids for 7 days. Biliary bile salts were measured by reverse-phase HPLC, and hydrophobicity indices were estimated by Heuman's method. Cholesterol absorption efficiency was determined by a plasma dual-isotope ratio method. In mice fed chow, natural proportions of tauro-beta-muricholate (42 +/- 6%) and taurocholate (50 +/- 7%) with a hydrophobicity index of -0.35 +/- 0.04 produced cholesterol absorption of 37 +/- 5%. Because bacterial and especially hepatic biotransformations of specific bile acids occurred, hydrophobicity indices of the resultant bile salt pools differed from fed bile acids. We observed a significant positive correlation between hydrophobicity indices of the bile salt pool and percent cholesterol absorption. The principal mechanism whereby hydrophilic bile acids inhibit cholesterol absorption appears to be diminution of intraluminal micellar cholesterol solubilization. Gene expression of intestinal sterol efflux transporters Abcg5 and Abcg8 was upregulated by feeding cholic acid but not by hydrophilic beta-muricholic acid nor by hydrophobic deoxycholic acid. We conclude that the hydrophobicity of the bile salt pool predicts the effects of individual fed bile acids on intestinal cholesterol absorption. Natural alpha- and beta-muricholic acids are the most powerful inhibitors of cholesterol absorption in mice and might act as potent cholesterol-lowering agents for prevention of cholesterol deposition diseases in humans.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2003

Hydrophilic bile salts have a cytoprotective effect against cyclosporine A-induced cholestasis through enhanced canalicular membrane fluidity and transporter activity.

Cyclosporine A (CsA) reduces liver canalicular membrane (CM) fluidity to cause a disproportionate reduction of biliary lipid secretion (the uncoupling phenomenon) without affecting adenosine triphosphate-dependent (ABC) transporters except for Mdr1. This study investigated whether hydrophilic bile salts inhibit CsA-induced cholestasis, focusing on CM fluidity and ABC transporter expression. Male Sprague-Dawley rats were infused with taurocholate (TC) (200 nmol/min/100 g body weight) for 2 h, flowed by infusion with tauroursodeoxycholate (TUDC), tauroalphamuricholate, or taurobetamuricholate (100 nmol/min/100 g body weight plus TC at 100 nmol/min/100 g body weight). Thereafter, CsA (20 mg/kg body weight) was injected as a bolus and bile was collected for 2 h. Canalicular membrane vesicles were prepared for analysis of cholesterol (CH), phospholipid (PL), CM fluidity, and expression of ABC transporters (Mdr1, Bsep, Mdr2, and Mrp2). CsA administration reduced biliary lipid secretion along with a disproportionately smaller decline of bile salt secretion. Hydrophilic bile salts significantly inhibited cholestasis after CsA injection by increasing CM fluidity and by increasing the expression of Mrp2 and Bsep, whereas Mdr1 and Mdr2 were unaltered. (1) Hydrophilic bile salts inhibit CsA-induced cholestasis, presumably by increasing CM fluidity, and this action was greatest with TUDC. (2) The fact that ABC transporters, except for Mdr1 and Mdr2, were overexpressed in the CM after infusion of these bile salts suggests that cytoprotective bile salts functions may increase transporter mass as well as enhancing transporter activity.

Journal Article↗
PubMed2003

Choleretic action of diosgenin is based upon the increases in canalicular membrane fluidity and transporter activity mediating bile acid independent bile flow.

It is known that diosgenin alters the lipid composition of hepatic plasma membranes as well as bile lipids. We recently reported that changes in the lipid composition of the canalicular membrane bilayer were associated with alterations of membrane fluidity. Therefore, the present study was performed to determine the effect of diosgenin on bile secretion, focusing on canalicular membrane composition, membrane fluidity, transporter expression, and transporter activity. METHODS: SD rats were fed a diet with or without diosgenin. Bile duct cannulation was done and the bile acid pool was depleted, followed by infusion of sodium taurocholate for 120 min to collect bile samples. Bile flow and the biliary output of cholesterol (Ch), phospholipids, bile salt, and total glutathione (GSH+GSSG) were estimated. Liver canalicular membrane vesicles (CMV) were prepared for the assessment of lipid composition, ATP-dependent transporters, and membrane fluidity. RESULTS: Bile flow, especially bile acid-independent fraction, was increased significantly by diosgenin. Biliary output of Ch and total glutathione were significantly increased by diosgenin. CMV fluidity and Mrp2 expression were increased by diosgenin. CONCLUSION: The fact that diosgenin increased bile flow and biliary cholesterol and glutathione output indicates a choleretic action along with enhancement of solute secretion. The increase of CMV fluidity and Mrp2 suggests that the choleretic action of diosgenin was based upon both the direct stimulation of transporter expression and indirect transporter activation by an increase of membrane fluidity.

Journal Article↗
PubMed2003

Unique reciprocal changes of hepatocellular membrane transporter expression and fluidity in rats with selective biliary obstruction.

BACKGROUND AND AIMS: The localized occlusion of bile ducts by intrahepaticlithiasis and intrahepatic neoplasms dose not cause severe jaundice, although the reason is unclear. The aim of this study was to clarify the molecular change of the liver in partial cholestasis, especially with respect to transporter expression (Mrp2, Mrp3, Bsep, P-gps) and membrane fluidity. METHODS AND RESULTS: After 3 days of selective bile duct ligation in Sprague-Dawley rats, the obstructed lobe (OL) and non-OL were analyzed. Canalicular and sinusoidal membrane fluidity were decreased in the OL compared with the non-OL. Mrp2 protein expression was significantly lower in the OL (by 62.9+/-6.9%) when compared with the non-OL. Mdr1b and Mdr2 mRNA were up-regulated in the OL when compared with the non-OL. Interestingly, Mrp3 protein and mRNA were induced in both the non-OL and OL of rats without hyperbilirubinemia. CONCLUSIONS: It seems that the reduction of membrane fluidity in the OL is a local response to localized cholestasis, while the induction of Mrp3 observed in both the OL and non-OL may be a response of the whole liver to localized impairment of bile secretion, although the regulatory mechanism is yet to be established.

Journal Article↗
PubMed2003

Unique inhibition of bile salt-induced apoptosis by lecithins and cytoprotective bile salts in immortalized mouse cholangiocytes.

Bile duct epithelium is physiologically exposed to high concentrations of bile salts, suggesting the presence of a cytoprotective mechanism(s). The aim of this study was to clarify whether bile salts cause bile duct cell damage and to elucidate the mechanism(s) providing protection against such an action of bile salts. Immortalized mouse cholangiocytes were incubated with taurocholate, taurochenodeoxycholate, glycochenodeoxycholate (GCDC), taurodeoxycholate, and tauroursodeoxycholate (TUDC), followed by flow-cytometric analysis and caspase activity assay to evaluate the induction of apoptosis. GCDC time-dependently induced caspase 3 (3.4-fold)- and caspase 9 (1.4-fold)-mediated apoptosis of cholangiocytes, but this was inhibited by lecithins and TUDC. Further, expression of cholangiocyte bile salt transporters (apical sodium-dependent bile salt transporter [Asbt] and multidrug resistance protein 3 [Mrp3]) was examined by RT-PCR and western blotting, and cholangiocyte bile salt uptake was determined using radiolabeled bile salts. Expression of cholangiocyte Asbt and Mrp3 was increased by bile salts, whereas lecithins interestingly reduced bile salt uptake to inhibit cholangiocyte apoptosis. In conclusion, bile salts themselves cause cholangiocyte apoptosis when absorbed by and retained inside the cell, but this is inhibited by washing out cytotoxic bile salts according to Mrp3, a rescue exporting molecule. Biliary lecithin is seemingly another cytoprotective player against cytotoxic bile salts, reducing their uptake, and this is associated with a reduced expression of Mrp3.

Animals↗
PubMed2003

Impaired gallbladder mucosal function in aged gallstone patients suppresses gallstone recurrence after successful extracorporeal shockwave lithotripsy.

BACKGROUND: Absorption of water, as well as emptying of bile, are important functions of the gallbladder. We studied the changes of gallbladder function with age in gallstone patients and their influence on the outcome of extracorporeal shockwave lithotripsy (ESWL). METHODS: (i) A total of 123 consecutive patients with complete stone clearance by ESWL were examined. Gallbladder emptying was assessed before treatment using intravenous cholecystography. After stone clearance, the recurrence of gallstones was monitored by using ultrasonography. Cox regression analysis was used to determine the risk factors associated with stone recurrence. (ii) Gallbladder bile was sampled from 59 gallstone patients during surgery. Biliary cholesterol, phospholipids, and total bile acids were simultaneously quantified by using gas-liquid chromatography. RESULTS: Impaired gallbladder function, but not gallstone recurrence, was more frequently observed in older patients (>/=65 years old) than in younger patients (<65 years old). Cox regression analysis revealed that poor gallbladder emptying was an independent predictor of stone recurrence after ESWL in the total study population, but not in the older patients (>/=65 years old). Analysis of bile from surgically treated patients with cholesterol stones showed a significantly higher total lipid concentration and a shorter nucleation time in the younger group (<65 years old), but the cholesterol saturation index did not differ between the younger and older groups. CONCLUSIONS: Our data suggest that the reduced concentrating function of the gallbladder in elderly gallstone patients helps to counteract stone recurrence despite their abnormal gallbladder motility. Therefore, aged gallstone patients may be preferentially treated by a non-surgical strategy.

Age Factors↗
PubMed2002

Less hydrophobic phosphatidylcholine species simplify biliary vesicle morphology, but induce bile metastability with a broad spectrum of crystal forms.

Cholesterol crystallization in bile is affected by phosphatidylcholine (PtdCho) hydrophobicity. The aim of the present study was to determine whether PtdCho species modulate the metastable-labile limit and equilibrium solubility of cholesterol in the micellar phase of bile, thereby altering the distribution of cholesterol to biliary lipid carriers and thus influencing cholesterol crystallization. Supersaturated model bile (with a cholesterol saturation index of 2.0 and a total lipid concentration of 10 g/dl) was prepared with various PtdCho/(bile salt+PtdCho) ratios (0.1-0.5) using egg yolk or soya bean PtdCho. Subsequently, the following features were determined: metastable-labile limit, equilibrium solubility of cholesterol, metastable zone, and cholesterol crystallization process. Less hydrophobic PtdCho species destabilized bile cholesterol to induce rapid crystallization, because of a broad integrated metastable zone, whereas more hydrophobic species stabilized bile cholesterol with a less integrated metastable zone and thus retarded cholesterol crystallization. Cholesterol crystallization was accelerated by a decrease in the PtdCho/(bile salt+PtdCho) ratio, whereas the final nucleated crystal mass was increased by an increase in this ratio. With decreasing hydrophobicity of the PtdCho species, the intermixed micellar/vesicular concentration of bile salts decreased in association with less formation of vesicles and increased formation of micelles, and a variety of crystal forms were detected. In conclusion, PtdCho species directly influenced the cholesterol crystallization process in model bile by remodelling the bile mesophase, and also had an indirect influence by altering the balance between bile salt micelles and vesicles.

Bile↗
PubMed2002

Cholesterol gallstones.

Cholesterol cholelithiasis is common in Western populations and represents a consequence of altered cholesterol homeostasis. Gallstones form because of a complex and incompletely understood series of metabolic and physicochemical events that promote cholesterol crystallization in bile. In the context of current paradigms, this article reviews recent progress in research on biliary lipid metabolism and the pathogenesis of cholesterol gallstones.

Journal Article↗