Bile and plasma lipid composition in non-obese normo-lipidemic subjects with and without cholesterol gallstones

ABSTRACT— A two-stage study was carried out to characterize the bile and plasma lipid composition in normolipidemic non-obese patients with and without cholesterol gallstones. The first stage involved 11 patients with cholesterol gallstones admitted for elective cholecystectomy and a control group of 16 patients without cholesterol gallstones undergoing elective laparotomy. Bile samples were obtained intraoperatively by aspiration from the gallbladder. The bile of all the gallstone patients was supersaturated with cholesterol and its nucleation time was much shorter than that of bile in the control group (2.5 days vs 22.5 days, respectively, P<0.001). The biliary fatty acid profile of phosphatidylcholine (PC) and free fatty acids (FFA) of gallstone patients was similar to that of the control group. C-22 fatty acids were found in a higher concentration in the FFA than in the PC fatty acids (P<0.05) in both groups of patients. Plasma triglyceride levels in the gallstone patients were significantly higher than those in the control group and the biliary cholesterol level correlated with that of plasma triglycerides. In the second stage of the study, plasma lipid profiles were obtained in two additional groups of patients, 20 patients with and 24 patients without cholesterol gallstones, for an in-depth characterization of the differences in plasma lipid profiles. The gallstone patients were found to have not only significantly higher concentrations of plasma triglycerides but increased cholesterol and phospholipid level as well. These differences were essentially due to a higher lipid content of the plasma VLDL fraction, similar to the pattern of patients with type IV hyperlipoproteinemia.     

Cisapride improves gallbladder emptying and bile lipid composition in patients with gallstones

BACKGROUND AND AIM: Biliary cholesterol supersaturation, gallbladder stasis and delayed intestinal transit are the key events in cholesterol gallstone formation. We studied the effect of cisapride, a prokinetic drug, on gallbladder emptying and bile composition in patients with gallstone disease undergoing cholecystectomy. METHODS: Gallbladder emptying, cholesterol saturation index (CSI) and nucleation time were studied in 21 patients with gallstone disease. Eleven patients (cisapride group, age 41.9 +/- 2.9 years) received tablet cisapride 10 mg t.i.d. for 2 weeks, while 10 patients (placebo group, age 42.1 +/- 1.9 years) received placebo for the same duration. Gallbladder emptying was repeated in all patients after a 2-week treatment with cisapride or placebo. Gallbladder bile was obtained at the time of surgery for the measurement of CSI and nucleation time. RESULTS: Residual volume of the gallbladder decreased (mean +/- SE, 18.6 +/- 2.5 mL vs 10.0 +/- 1.1 mL, P = 0.007), and the ejection fraction increased (43.5 +/- 5.3% vs 60.0 +/- 3.2%, P = 0.007) in patients in the cisapride group, while no change was observed in placebo group patients. Nucleation time was higher in the cisapride group than in the placebo group (14.9 +/- 1.3 days vs 8.0 +/- 0.9 days, P = 0.003). Patients in the cisapride group had a significantly lower cholesterol concentration (molar percentage, 5.1 +/- 0.3% vs 6.8 +/- 0.8%, P = 0.049) and CSI (1.0 +/- 0.1 vs 1.36 +/- 0.11, P = 0.034) than patients in the placebo group. CONCLUSION: Cisapride improves gallbladder emptying and bile lithogenicity in patients with gallstone disease.     

Measurement of apolipoprotein A1 in cholesterol gallstones and gallbladder bile of patients with gallstones

Biliary apolipoprotein A1 in bile inhibits the nucleation of cholesterol crystals from bile supersaturated with cholesterol. In the present study, using an enzyme-linked immunosorbent assay of apolipoprotein Al, we determined the content of apolipoprotein Al in cholesterol gallstones and samples of gallbladder bile collected simultaneously from 23 patients during cholecystectomy. Protein content in cholesterol gallstones ranged from 50 to 5700 g/g, with median, quartile, and three quartile values being 250, 111, and 740; apolipoprotein A1 content ranged from 9 to 9000 ng/g (200, 41, 647). The gallbladder bile samples contained protein at concentrations of 0.4-9.0 mg/ml (2.0, 1.1, 3.2), while apolipoprotein A1 was present at concentrations of 2.0-136.0 g/ml (30.0, 10.0, 90.0). A notable finding was that the A1/total protein (TP) values for gallbladder bile, which ranged from 0.13% to 6.80% (1.62, 0.89, 3.34), were several times higher than those determined for gallstone samples, which ranged from 0.01% to 1.2%, 2% (0.06, 0.02, 0.25). The results of sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed that the protein profile in cholesterol gallstones was similar to that in gallbladder bile. It was concluded that: (1) the protein contained in gallstones may originate from bile, (2) the content of apolipoprotein A1 in cholesterol gallstones is only a trace amount, compared with that in gallbladder bile, and (3) biliary apolipoprotein A1 may be retained in a soluble phase in gallbladder bile, with minimal precipitation onto the surfaces of gallstones.     

Antilithiasic and hypocholesterolemic effects of diets containing autoclaved amylomaize starch in hamster

The prevention of cholelithiasis by dietary manipulation was investigated in hamsters receiving a fat-free lithogenic (L) diet or this diet in which sucrose was replaced by 12 (group AS₁₂), 36 (group AS₃₆), 48 (group AS₄₈), or 72.5% (group AS_72.5) of autoclaved amylomaize starch for seven weeks. All hamsters (6/6) had cholesterol gallstones in groups L and AS₁₂, while only 3/6 hamsters in group AS₃₆ had gallstones. None were present in groups AS₄₈ and AS_72.5. Excent in group AS₁₂, biliary cholesterol level and lithogenic index, (LI) decreased significantly in hamsters receiving amylomaize starch. Plasma cholesterol concentration was reduced by 31 and 54%, respectively, in groups AS₄₈ and AS_72.5 as compared to group L. The concentration of esterified cholesterol in the liver was also reduced significantly in all groups receiving amylomaize starch. Hepatic cholesterogenesis was decreased by 74 and 65%, respectively, in groups AS₄₈ and AS_72.5 as compared to group L. The transformation of cholesterol to bile acids was increased in group AS_72.5 (+152%) as compared to L, while fecal cholesterol excretion was strongly lowered (–31%). Amylomaize starch reduced the microbial transformation of cholesterol to coprosterol and epicoprosterol, and in group AS_72.5 it decreased the degradation of cholic acid. Thus, this autoclaved amylomaize starch, which could be used in human nutrition, prevents cholelithiasis and lowers cholesterolemia.This investigation was supported by a C.R.E. grant awarded by INSERM and Caisse Régionale d'Assurance Maladie de l'Ile de France.     

Mucin and phospholipids determine viscosity of gallbladder bile in patients with gallstones

AIM: An increased viscosity of gallbladder bile has been considered an important factor in the pathogenesis of gallstone disease. Besides lipids and proteins, mucin has been suggested to affect the viscosity of bile. To further clarify these issues we compared mucin, protein and the lipid componEnts of hepatic and gallbladder bile and its viscosity in patients with gallstones. METHODS: Viscosity of bile (mPa.s) was measured using rotation viscosimetry in regard to the non Newtonian property of bile at low shear rates. RESULTS: Biliary viscosity was markedly higher in gallbladder bile of patients with cholesterol (5.00 +/- 0.60 mPa.s, mean +/- SEM, r= 28) and mixed stones (3.50 +/- 0.68 mPa.s; r= 8) compared to hepatic bile (0.92 +/- 0.06 mPa.s, r= 6). A positive correlation between mucin and viscosity was found in gallbladder biles (r = 0.65; P < 0.001) but not in hepatic biles. The addition of physiologic and supraphysiologic amounts of mucin to gallbladder bile resulted in a dose dependent non linear increase of its viscosity. A positive correlation was determined between phospholipid concentration and viscosity (r = 0.34, P < 0.005) in gallbladder biles. However, no correlation was found between total protein or the other lipid concentrations and viscosity in both gallbladder and hepatic biles. CONCLUSION: The viscosity of gallbladder bile is markedly higher than that of hepatic bile in patients with gallstones. The concentration of mucin is the major determinant of biliary viscosity and may contribute by this mechanism to the role of mucin in the pathogenesis of gallstones.     

Gallbladder stone recurrence after medical treatment do gallstones recur true to type?

Medical treatments that dissolve or remove gallbladder stones but leave the gallbladder in situ have the disadvantage of gallstone recurrence. Little is known about the composition of recurrent stones or whether they recur true to type. In 21 patients with recurrent stones detected 5–74 months (mean ±sem, 26±4 months) after being rendered stone-free with dissolution therapy (N=15) or percutaneous cholecystolithotomy (N=6), we compared pretreatment and postrecurrence gallstone number, maximum gallstone attenuation scores measured by computed tomography (CT) and, in 13, the dissolvability of the recurrent stones with oral bile acids ± extracorporeal shock-wave lithotripsy. Before treatment, five patients had solitary and 16 had multiple stones but on recurrence, the gallstones differed in number from the primary stones in 10 of the 21 patients. As a result of patient selection, before dissolution, the primary stones were all radiolucent with maximum CT scores of <100 Hounsfield units (HU) (mean 45, range 10–84 HU). On recurrence, the stones were again CT-lucent in 13 of the 15 patients but were CT-dense in the remaining two (118 and 176 HU). Initially, all six patients treated by percutaneous cholecystolithotomy had radio-opaque stones, with a mean CT score of 459 (range 100–969) HU. However, on recurrence, only one had calcified stones (HU 140); the remaining five had CT-lucent stones (16–98 HU,P<0.05). Of the 13 patients whose recurrent, plain x-ray-lucent and CT-lucent stones were treated with oral bile acids ± lithotripsy, 12 (92%) showed evidence of gallstone dissolution. We conclude that gallbladder stones do not recur true to type in up to two thirds of patients. However, irrespective of original gallstone composition, recurrent stones are usually radio- and CT-lucent, presumed cholesterol-rich, and therefore potentially dissolvable with oral bile acids.     

Bile acids in serum and bile of patients with cholesterol gallstone

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Differences in phosphatidylcholine and bile acids in bile from Egyptian and UK patients with and without cholangiocarcinoma

Background

Cholangiocarcinoma (CC) is a fatal malignancy, the incidence of which is increasing worldwide, with substantial regional variation. Current diagnostic techniques to distinguish benign from malignant biliary disease are unsatisfactory. Metabolic profiling of bile may help to differentiate benign from malignant disease. No previous studies have compared the metabolic profiles of bile from two geographically and racially distinct groups of CC patients.

Objectives

This study aimed to compare metabolic profiles of bile, using in vitro proton magnetic resonance spectroscopy, from CC patients from Egypt and the UK, and from patients with CC and patients with non-malignant biliary disease.

Methods

A total of 29 bile samples, collected at cholangiography, were analysed using an 11.7-T system. Samples were from eight CC patients in either Egypt (n = 4) or the UK (n = 4) and 21 patients with benign biliary disease (choledocholithiasis [n = 8], sphincter of Oddi dysfunction [n = 8], primary sclerosing cholangitis [n = 5]).

Results

Bile phosphatidylcholine (PtC) was significantly reduced in CC patients. Egyptian CC patients had significantly lower biliary PtC levels compared with UK patients. Taurine- and glycine-conjugated bile acids (H-26 and H-25 protons, respectively) were significantly elevated in bile from patients with CC compared with bile from patients with benign diseases (P = 0.013 and P < 0.01, respectively).

Conclusions

Biliary PtC levels potentially differentiate CC from benign biliary disease. Reduced biliary PtC in Egyptian compared with UK patients may reflect underlying carcinogenic mechanisms.     

Effect of cholestyramine treatment on biliary lipid secretion rates in normolipidaemic men

This study was designed to clarify the effect of bile acid sequestrant treatment on the total biliary output rates of cholesterol, phospholipids and bile acids in man, and to correlate these changes with the alterations in plasma lipoprotein levels. For this purpose nine healthy, normolipidaemic men were treated with 16 g of cholestyramine daily over a period of 4 weeks, and the biliary secretion rates were measured by a duodenal perfusion technique. Resin therapy, which profoundly increases de novo synthesis of bile acids, resulted in a lowering of total plasma cholesterol levels, mainly due to a 35% reduction in low density lipoprotein (LDL) cholesterol, and in a 33% increase in plasma triglyceride levels, reflecting enhanced very low density lipoprotein (VLDL) triglyceride concentrations; high density lipoprotein (HDL) levels did not change. However, these lipoprotein changes did not correlate with any alterations in biliary lipid output. Total hepatic secretion rates of the biliary lipids remained generally unchanged during treatment, with a tendency towards lower cholesterol output, resulting in a lower molar percentage of cholesterol in hepatic bile, 3.4 +/- 0.4 vs. 2.9 +/- 0.2 mol %. This is probably due to an increased rate of conversion of cholesterol to bile acids in the hepatocyte. It is concluded that, in man, the liver may adapt well to changes in the enterohepatic circulation of bile acids, thereby maintaining output rates of biliary lipids at a relatively constant level.     

Qualitative and quantitative comparison of gallbladder proteins from patients with and without cholesterol gallstones

Amino acid analysis and protein electrophoretic techniques were used to determine whether qualitative and quantitative gallbladder protein abnormalities exist in patients with cholesterol gallstones in Inner Mongolia. Gallbladder bile osmotic pressure measurement was determined and correlations were sought between the protein concentration and osmotic pressure of gallbladder bile. Protein concentrations and bile osmolality were higher in patients with cholesterol gallstones than in controls without biliary tract disease. A correlation between the protein concentration and osmotic pressure was found in gallbladder patients but not in controls (patients: r=0.83, P<0.05; controls: r=0.74, P<0.1).     

Impaired absorption of cholesterol and bile acids in patients with an ileoanal anastomosis

Background—No data exist on cholesterolabsorption in patients with an ileoanal anastomosis (IAA).
Aims—To study cholesterol absorption and itseffects on cholesterol and bile acid metabolism in patients with an IAA.
Patients and methods—Cholesterol absorption, andserum, biliary, and faecal lipids were studied in 24 patients with anIAA and 20controls.
Results—Fractional cholesterol absorption wassignificantly lower in the patients (36% versus 47% in controls).Surprisingly, the calculated intestinal influx of endogenouscholesterol was reduced so that the absolute absorption of cholesterolwas decreased; elimination of cholesterol as faecal neutral steroidsremained normal. Thus, the slightly increased cholesterol synthesis was mainly due to increased faecal bile acid excretion, which, in turn, wasassociated with reduced absorption and biliary secretion of bile acids.Serum total and low density lipoprotein (LDL) cholesterol and LDLtriglycerides were lower in the patients. Molar percentage andsaturation index of biliary cholesterol were slightly higher inpatients with an IAA. Proportions of secondary bile acids in bile andfaeces were diminished, and faecal unidentified bile acids were higherin patients.
Conclusions—Cholesterol absorption issignificantly impaired in patients with an IAA, and is closely relatedto changes in serum and biliary lipids observed in these patients.

Keywords:cholesterol absorption; cholesterol synthesis; faecal bile acids; inflammatory bowel disease

     

Lovastatin alters biliary lipid composition and dissolves gallstones: a long-term study in prairie dogs

Lovastatin, an inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, is widely used to treat hypercholesterolemia. We investigated the long-term effects of lovastatin alone and in combination with ursodeoxycholic acid on biliary lipid composition and gallstone dissolution. Forty-two prairie dogs were fed 1.2% cholesterol diet for 5 weeks, and cholecystectomy was performed on 6 animals to confirm gallstones. The remaining animals were maintained on a 0.4% cholesterol diet and were randomized to receive placebo, lovastatin (3.3 mg/g diet), ursodeoxycholic acid (10 mg/g), or combination of both drugs. After 10 weeks, animals underwent cholecystectomy. Dissolution response to therapy was determined, and serum and biliary lipids were measured. All treatment groups had significant reductions in serum cholesterol. Lovastatin treatment reduced both hepatic and gallbladder bile cholesterol, altered bile acid composition, and induced a 79% total response compared to placebo. Although ursodeoxycholic treatment induced a 44% response, long-term combination treatment elevated both gallbladder bile cholesterol and calcium and failed to produce an augmented response. These data suggest that lovastatin therapy alone may promote gallstone dissolution in humans.     

Serum bile acid levels as a predictor for the severity of liver fibrosis in patients with chronic hepatitis C

Summary. Serum bile acids (SBAs) are commonly elevated in cholestatic liver diseases, but it is unclear if SBA levels are also elevated in noncholestatic chronic liver diseases and whether those levels correlate with disease severity. We analysed SBA levels of 135 consecutive patients with chronic hepatitis C virus infection and correlated these levels with the degree of liver fibrosis as determined by liver biopsy. In addition, we assessed the accuracy of SBA levels as a noninvasive predictor for liver fibrosis by its comparison to the patients’ FibroTest scores. Two‐thirds (90/135 patients, 67%) of the study patients had nonsevere liver fibrosis (Metavir F0–F2), and the others (45/135, 33%) had severe fibrosis or cirrhosis (Metavir F3–F4). The SBA levels were significantly higher in patients with severe fibrosis as compared to nonsevere fibrosis (11.46 ± 10.01 vs 6.37 ± 4.69, P < 0.0001). Furthermore, a receiver operator characteristics curve based on a model that included serum bile acids, age, body mass index, serum AST, glucose and cholesterol levels suggested that this combination reliably predicts the degree of liver fibrosis and is not inferior to the current noninvasive FibroTest score (areas under the curve of 0.837 vs 0.83, respectively, P = 0.87). We conclude that measurement of SBA levels may have a clinical role as a simple noninvasive tool to assess the severity of HCV‐induced liver disease. Combined with widely available laboratory parameters, SBA levels can predict disease severity with a high degree of accuracy.     

A multicenter comparison of nicorandil and diltiazem on serum lipid,apolipoprotein, and lipoprotein levels in patients with ischemic heart disease

Summary The effects of nicorandil and diltiazem on serum lipid, apolipoprotein, and lipoprotein levels in 37 patients with ischemic heart disease were examined in a randomized, multicenter study. Nicorandil (n=20, 10–40 mg/day, b.i.d.) and diltiazem (n=17, 60–240 mg/day, b.i.d.) were administered for 12 weeks. Both nicorandil and diltiazem administration showed an effective antianginal effect. Diltiazem administration showed a significant hypotensive action. There were no significant changes in serum lipids, apolipoproteins, and lipoproteins for both nicorandil and diltiazem. There were no significant changes in body weight, uric acid, and fasting blood sugar levels during the test period for both drugs. These data show that nicorandil, like diltiazem, does not have any adverse effects on lipid metabolism and that it is a favorable drug to use as an agent for treating arteriosclerotic heart disease.This paper was presented, in part, at the 3rd Cardiovascular Pharmacotherapy International Symposium, October 15–19, 1989, Kyoto, Japan.     

Changes of lipid metabolism in plasma, liver and bile during cholesterol gallstone formation in rabbit model

AIM To find out the relationship between the disturbances of lipid metabolism and the formation of cholesterol gallstones by studying the changes of lipid metabolism in plasma, liver tissue and the bile.METHODS Male and female white Japanese rabbits were divided randomly into a control group (Con) and four experimental groups of 10 rabbits each fed with a diet containing 1.2% cholesterol for one, two, three and four weeks (1wk, 2wk, 3wk and 4wk group). The measurement of plasma triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and its subfractions (HDL2-C, HDL3-C), very low and low density lipoprotein cholesterol (VLDL-C, LDL-C) was taken with standard enzymatic techniques. Apolipoprotein (apo) concentrations in plasma were measured by radial immunodiffusion assay for apoA1, apoB100, aopCⅡ and apoCⅢ. Total cholesterol of liver was measured by the enzymatic procedure for each animal. Bile acids, mainly glycocholate (GCA) and glycodeoxycholate (GDCA) were detected by dual wavelength thin layer scanner.RESULTS In all the experimental groups fed with dietary cholesterol, cholesterol crystal was found in the gallbladder in 2/10 cases of the 1wk group, 4/10 of the 2wk group, 6/10 of the 3wk group and 7/10 of the 4wk group respectively. The concentration of plasma total cholesterol (TC), triglyceride (TG), phospholipid (pl), VLDL-C, LDL-C, apoB100, apoCⅡ, apoCⅢ gradually increased (P＜0.05) with the prolonged feeding time of dietary cholesterol. High density lipoprotein cholesterol and its subfractions (HDL-C, HDL2-C, HDL3-C) showed a tendency to decrease, but without statistical significance (P＞ 0.05). ApoA1 was reduced with increased feeding time of dietary cholesterol (P ＜0.05). The hepatic and biliary cholesterol increased 1-1.5 times as compared with the control group (t=5.221 and 3.445, P＜0.05). The GCA gradually decreased beginning from the control group to the 4wk group (P＜0.05).CONCLUSION Owing to the high cholesterol diet, the increased concentrations of plasma TC, TG, VLDL-C, LDL-C, hepatic TC and TG, apoB100, apoCⅡ and apoCⅢ possibly enhanced the secretion of biliary cholesterol into bile; the decreased plasma apoA1 level might reduce the secretion of antinucleating factor into bile. All those factors mentioned above probably contribute to the formation of cholesterol gallstones.     

Biliary lipid composition in idiopathic bile acid malabsorption

Background—Chronic diarrhoea is the clinicalhallmark of patients presenting with idiopathic bile acidmalabsorption. Its pathogenesis is unknown; colonic water secretion canbe induced by dihydroxy bile acids, but it is not known whetherenrichment of the bile acid pool with these bile acids occurs in suchpatients. Furthermore, bile acid malabsorption is known to affectbiliary lipid composition, but no information is available for theidiopathic type.
Aims—To verify: (a) whetherdiarrhoea in patients with idiopathic bile acid malabsorption isassociated with enrichment of the bile acid pool with dihydroxy bileacids; and (b) whether supersaturation with cholesterol ofduodenal bile occurs in such patients as a result of chronic bile acid depletion.
Patients—Thirteen patients with idiopathic bileacid malabsorption diagnosed according to abnormal ⁷⁵SeHCATtest and absence of other organic diseases, and 23 control subjects.
Methods—Bile rich duodenal fluid was collectedduring intravenous ceruletide infusion in the fasting state. Biliarylipids were analysed by enzymatic assays and bile acids by highperformance liquid chromatography.
Results—Patients with idiopathic bile acidmalabsorption had a cholesterol saturation index similar to controls.Bile acid composition showed only a decrease in percentage cholic acid(29(2)% versus 36 (2)%; p<0.05); the dihydroxy:trihydroxy bile acid ratio was similar to controls.
Conclusions—Patients with idiopathic bile acidmalabsorption do not have an increased risk of forming cholesterolgallstones. The mechanism of diarrhoea does not seem to depend on anenrichment of the bile acid pool with dihydroxy bile acids.

Keywords:primary bile acid malabsorption; bile acids; diarrhoea; ⁷⁵SeHCAT; biliary lipids; cholesterol saturationindex

     

Association of lipoprotein(a) levels and apolipoprotein(a) phenotypes with coronary artery disease in Type 2 diabetic patients and in non-diabetic subjects.

AIMS: We investigated whether in Type 2 diabetic patients lipoprotein(a) (Lp(a)) levels and apolipoprotein(a) (apo(a)) polymorphism are associated with angiographically documented coronary artery disease (CAD). We also examined whether there are differences in the distributions of Lp(a) levels and apo(a) phenotypes between CAD patients with and without diabetes. METHODS: A hundred and seven diabetic patients with CAD, 274 diabetic patients without CAD, 201 non-diabetic patients with CAD, and 358 controls were enrolled. RESULTS: Diabetic patients with CAD showed Lp(a) levels (21.2 +/- 17.7 vs. 15.1 +/- 17.8 mg/dl; P = 0.0018) and a percentage of subjects with at least one apo(a) isoform of low molecular weight (MW) (67.2% vs. 27.7%; P = 0.0000) significantly greater than diabetic patients without CAD. Multivariate analysis showed that in diabetic patients Lp(a) levels and apo(a) phenotypes were significantly associated with CAD; odds ratios (ORs) of high Lp(a) levels for CAD were 2.17 (1.28-3.66), while ORs of the presence of at least one apo(a) isoform of low MW were 5.35 (3.30-8.60). Lp(a) levels (30.2 +/- 23.7 vs. 21.2 +/- 17.7 mg/dl; P = 0.0005) and the percentage of subjects with at least one apo(a) isoform of low MW (87.0% vs. 67.2%; P = 0.0001) were significantly higher in CAD patients without than in those with diabetes. CONCLUSIONS: Our data suggest that Lp(a) levels and apo(a) phenotypes are independently associated with CAD in Type 2 diabetic patients; thus both these parameters may be helpful in selecting diabetic subjects at high genetic cardiovascular risk. However, Lp(a) levels and apo(a) polymorphism seem to be cardiovascular risk factors less important in diabetic than in non-diabetic subjects. Diabet. Med. 18, 589-594 (2001)     

Cholangiocyte bile salt transporters in cholesterol gallstone-susceptible and resistant inbred mouse strains

Background and Aim: We investigated the dietary and gender influences on the expression and functionality of cholangiocyte bile salt transporters and development of biliary hyperplasia in cholesterol gallstone‐susceptible C57L/J and resistant AKR/J mice. Methods: C57L and AKR mice were fed chow, a lithogenic diet, or a cholic acid‐containing diet for 14 days. Expression of cholangiocyte bile salt transporter proteins ASBT (SLC10A2), ILBP (FABP6), and MRP3 (ABCC3) were studied by Western blot analysis. Taurocholate uptake studies were performed using microperfusion of isolated bile duct units. The pre‐ and post‐perfusion taurocholate concentrations were analyzed by high performance liquid chromatography. Biliary proliferation in liver sections was scored. Results: The lithogenic diet induced ductular proliferation in C57L mice. On chow, SLC10A2 and ABCC3 were overexpressed in male and female C57L compared to AKR mice. A lithogenic diet reduced the expressions of FABP6 in both male and female C57L mice, SLC10A2 in female C57L mice, and ABCC3 in male C57L mice. These alterations in transporter expressions were not associated with changes in taurocholate uptake. The lithogenic diet induced biliary hyperplasia and reduced bile salt transporter expressions in C57L mice. Conclusions: Although bile salt uptake was not increased in the bile duct unit, we speculate that the biliary hyperplasia on the lithogenic diet may lead to an increase in intrahepatic bile salt recycling during cholesterol cholelithogenesis.     

血清结合胆汁酸诊断脂肪肝

目的为脂肪肝患者实验室检查诊断提供有效的依据。方法采用反相高效液相色谱法（ＨＰＬＣ）检测３０例脂肪肝患者的血清７种结合胆汁酸，并以３０例无脂肪肝者作为对照。结果脂肪肝患者血清７种结合胆汁酸均高于无脂肪肝者（Ｐ＜０．０１）。结论血清结合胆汁酸有助于了解脂肪肝患者肝细胞病变程度，为早期诊治提供依据