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PubMed2005

VPAC1 expression is regulated by FXR agonists in the human gallbladder epithelium.

Vasoactive intestinal peptide receptor-1 (VPAC1) is the high-affinity receptor of vasoactive intestinal peptide (VIP), a major regulator of bile secretion. To better define the level at which VPAC1 stimulates bile secretion, we examined its expression in the different cell types participating in bile formation (i.e., hepatocytes, bile duct, and gallbladder epithelial cells). Because VPAC1 expression was previously shown to be regulated by nuclear receptors, we tested the hypothesis that it may be regulated by the farnesoid X receptor (FXR). Quantitative RT-PCR and immunoblot analyses of cell isolates indicated that VPAC1 is expressed in all three cell types lining the human biliary tree, with predominant expression in the gallbladder. In primary cultures of human gallbladder epithelial cells, VIP induced cAMP production and chloride secretion. Analysis of the VPAC1 gene revealed the presence of potential FXR response element sequences, and both FXR and RXRalpha expressions were detected in gallbladder epithelial cells. In these cells, the FXR pharmacological agonist GW4064 upregulated VPAC1 expression in a dose-dependent manner, and this effect was antagonized by the RXRalpha ligand, 9-cis retinoic acid. Chenodeoxycholate activated endogenous FXR in gallbladder epithelial cells, as ascertained by electromobility shift assay and upregulation of the FXR target gene, small heterodimer partner. Chenodeoxycholate also provoked an increase in VPAC1 mRNA and protein content in these cells. In conclusion, FXR agonists may increase gallbladder fluid secretion through transcriptional activation of VPAC1, which may contribute to the regulation of bile secretion by bile salts and to a protective effect of FXR pharmacological agonists in gallstone disease.

Base Sequence↗

PubMed1996

The role of gallbladder emptying in gallstone formation during diet-induced rapid weight loss.

Obese persons are at risk for cholesterol gallstones because their bile is saturated with cholesterol. The risk increases during rapid weight loss by means of certain very-low-calorie diets or gastric bypass surgery. Gallstone risk factors during rapid weight loss include increased bile cholesterol saturation index and gallbladder stasis. Obese subjects were randomized to one of two low-calorie liquid diets for rapid weight loss: a 520-kcal diet with less than 2 g fat/d, and a 900-kcal diet with 30 g fat/d (including one 10-g fat meal to stimulate maximal gallbladder emptying). Bile and blood lipids, saturation index, leukocyte 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity, and ultrasonographic gallbladder emptying were measured repeatedly during dietary treatment. Both diets produced comparable weight loss of 22%. Bile cholesterol saturation index increased during both diets (26%), but fell to 15% below prediet level after weight loss. Compared with subjects' maximal gallbladder emptying fraction of 66%, the 520-kcal diet provided poor gallbladder emptying (35%), whereas the 10-g fat meal of the 900-kcal diet provided maximal emptying. Gallstones developed in four of six 520-kcal subjects and none of seven 900-kcal subjects (P = .021), an unanticipated difference that resulted in premature study termination for ethical reasons. Blood lipids and HMG CoA reductase activity in mononuclear leukocytes fell at week 8 during both diets, but recovered while weight was still being lost. The findings suggest that gallstone risk during rapid weight loss may be reduced by maintenance of gallbladder emptying with a small amount of dietary fat. Ultimately, weight loss reduced bile cholesterol saturation and improved highdensity lipoprotein (HDL) levels.

Adult↗

PubMed1996

Apolipoprotein E4 genotype and gallbladder motility influence speed of gallstone clearance and risk of recurrence after extracorporeal shock-wave lithotripsy.

Extracorporeal shock-wave lithotripsy (ESWL) is an effective treatment in selected gallstone patients, but stone recurrence is a major drawback. Factors potentially influencing gallstone clearance and recurrence were studied in 84 patients in whom stone dissolution was diagnosed after ESWL plus bile salt therapy for initial solitary (n = 55) or multiple (n = 29) radiolucent stones. Apolipoprotein E (apoE) genotyping and gallbladder motility (sonography) were studied in a representative subgroup of patients (n = 50). The median follow-up after ESWL was 36 months (range, 4.5-67 months). Gallstone clearance was achieved after 8.7 months (range, 0.2-30 months). Independent factors significantly enhancing gallstone clearance were the presence of E4 allele; small initial gallstone size and number; effectiveness of fragmentation; and good gallbladder emptying (P = .002). Gallstone recurrence was seen in 30 patients after 18.6 months (range, 1.0-50 months). Cumulative gallstone recurrence rate (life-table analysis) was 15% within 1 year, increasing to 60% within 5.5 years. Although the probability of gallstone recurrence tended to be smaller in patients with initial solitary stones than in those with multiple stones during early follow-up, differences disappeared after long-term follow-up. Effective gallbladder emptying (residual volume < or = 6 mL) and apolipoprotein E4 (apoE4) independently influenced gallstone recurrence. Recurrence rate was higher (log rank test, P = .037) in those patients who were homozygous and heterozygous for the E4 allele compared with the individuals who were not expressing the apoE4 allele. Accordingly, there was an overrepresentation of the allele frequency for E4 in the group with gallstone recurrence (P =.03). Patients with small postprandial residual gallbladder volumes (</= 6 mL) had a lower probability of stone recurrence than those with large residual gallbladder volumes (log rank test, P = .0215). Biliary pain was more frequent with recurrence (55% vs. 13%, P = .001). The present study indicates that apoE4 genotype is associated with increased speed of gallstone clearance as well as a high risk of recurrence after ESWL. This finding points to a possible role for genetic factors in the pathogenesis of cholesterol gallstones. Effective gallbladder emptying is important for speed of clearance and prevention of recurrence. Patients with initial solitary stones have a decreased early- but not long-term gallstone recurrence rate.

Adult↗

PubMed2002

Expression of cyclooxygenase-2 in the subserosal layer correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder.

Postsurgical recurrence at distant sites frequently occurs in pathological tumor stage 2 (pT(2)) carcinoma of the gallbladder even though the carcinoma is limited to the gallbladder wall. Little is known, however, about the molecular events leading to its development and progression. A large body of evidence suggests that cyclooxygenase-2 (COX-2) is up-regulated in carcinoma tissues and plays roles in promoting cell-proliferation, growth and metastasis of carcinoma cells. In the present study, immunohistochemistry was performed to determine the expression levels of COX-2 in the subserosal layer of 33 cases of pT(2) gallbladder carcinoma in which curative resections had been performed and to determine the correlations of the expression levels of COX-2 with mode of recurrence and postsurgical survival. Immunostaining of COX-2 in the epithelia was recognized in more than 80% of normal epithelia, noncancerous pathological lesions of the gallbladder except for intestinal metaplasia and pT(1-4) carcinoma specimens. Intense staining was observed in large percentages of hyperplastic lesions (65%), pT(2) carcinoma specimens (76%) and pT(3) and pT(4) carcinoma specimens (64%) compared to the percentages of normal epithelia and other pathological lesions (0-25%). Intense staining was also observed in the adjacent stroma in pT(2) carcinoma specimens (33%) and in those in pT(3) and pT(4) carcinoma specimens (43%) but only in small percentages of the stroma adjacent to normal epithelia and pathological lesions (0-8%). In situ hybridization confirmed the existence of COX-2 mRNA in both the cancerous epithelia and adjacent stroma of pT(2)-pT(4) carcinomas. In 33 cases of pT(2) carcinoma, distant recurrence, i.e., liver metastasis, was seen in 3 of 9 cases of pT(2) carcinoma (33%, P<0.05) with intense stromal staining in the subserosal layer and in 1 of 24 cases (4%) without intense staining, whereas no significant correlation was found between parameters of pathological malignancies (histological grade, lymphatic permeation, venous permeation and lymph node metastasis) and the intensity of stromal staining in the subserosal layer. The postsurgical survival outcome was significantly poorer in the former than in the latter (p = 0.010). In pT(2) gallbladder carcinoma, upregulation of COX-2 in the stroma adjacent to the cancerous epithelia in the subserosal layer correlates with the aggressiveness of the disease, such as the tendency to form distant recurrences. This phenotype may serve as a unique biological feature associated with the malignant behavior of pT(2) gallbladder carcinoma.

Adult↗

PubMed1987

Gallbladder wall thickening: a frequent finding in various nonbiliary disorders--a prospective ultrasonographic study.

A comprehensive prospective ultrasonographic study was performed in 93 patients to investigate gallbladder wall thickness and gallbladder volumes in various nonbiliary disease states. Without changes in gallbladder volume, mean gallbladder wall thickness was significantly increased (p less than 0.01) in patients with liver cirrhosis, viral hepatitis, chronic congestive heart failure, hypoalbuminemia, and chronic renal failure (p less than 0.05) but not in patients with diabetes mellitus (n = 14) as compared to a control group. The present study confirms that a variety of nonbiliary disorders are associated with significant thickening of gallbladder walls and that this finding is not caused by incomplete gallbladder contraction.

Diabetes Mellitus↗

PubMed2005

Monitoring of gallbladder and gastric coordination by EPI.

PURPOSE: To assess for the first time the potential of echo-planar magnetic resonance imaging (EPI) for measuring simultaneously both gallbladder and gastric emptying. MATERIALS AND METHODS: Eight healthy subjects ingested 500 mL of an acid-stable liquid test meal containing 15% olive oil and flavoring. Every 20 minutes for three hours thereafter, a rapid EPI multislice set was acquired across the whole abdomen, using a dedicated whole-body 0.5-T EPI scanner. RESULTS: The bile in the gallbladder and the test meal in the stomach appeared bright in the EPI images, aiding localization and region of interest analysis. We measured the gallbladder emptying curve and fitted the data to a simple analytical model. The mean fasted gallbladder volume was 25 +/- 4 mL, comparable to previously published MRI and ultrasound values. Gastric emptying data fitted well to a linear model linear (R2 = 0.99), and we observed an exponential (R2 = 0.98) relationship between gallbladder and gastric volumes for the first 90 minutes. CONCLUSION: This study shows the potential of EPI to monitor simultaneously and noninvasively the emptying of the gallbladder and of the gastric lumen. No contrast enhancing agents are needed. This method could overcome the limitations of previous gamma scintigraphy and ultrasound techniques.

Echo-Planar Imaging↗

PubMed2005

Laparoscopic cholecystectomy for treatment of unexpected early-stage gallbladder cancer.

BACKGROUND AND OBJECTIVES: Laparoscopic cholecystectomy (LC) may result in the incidental diagnosis of early stage (T1 and T2) gallbladder cancer. LC is useful for T1 patients, however, its role in T2 patients remains controversial. We sought to determine the effect of initial LC on patient outcome in early-stage gallbladder cancer. METHODS: Twenty-nine patients with T1 or T2 disease were reviewed retrospectively to assess preoperative diagnosis, intraoperative findings, and outcomes. RESULTS: Diagnoses included gallbladder stones (5), gallstones with polyps (5), and gallbladder polyps (19). Malignancy was suspected in 15 patients (14 polyp lesions and 1 gallbladder stone with wall thickening). After frozen sections, two T2 patients were immediately treated with radical operation owing to positive margins. Of 14 patients diagnosed by pathology, 4 T2 patients with positive margins underwent a second radical operation. Five-year survival rate was 100% and 49.6 % (T1 and T2 patients). No mortality or recurrence was detected in T1 patients (mean follow-up, 45.8 months; range, 6-98 months). Three T2 patients died, and one T2 patient relapsed after LC. No port site metastasis was detected. CONCLUSIONS: LC for T1a and T1b gallbladder cancer needs no additional treatment, however, radical operation for T2 patients is recommended, regardless of the margin condition.

Cholecystectomy, Laparoscopic↗

PubMed2006

Environmental pollutants in gallbladder carcinogenesis.

Gallbladder cancer is a common malignancy of the gastrointestinal tract that shows wide geographical variation in its distribution. Cause of gallbladder cancer is still obscure; however, various etiological factors have been proposed. Of these gallstones and inflammation of the gallbladder is commonest. Despite three decades of active research no conclusive evidence is available as to what causes gallbladder cancer? In this article we reviewed the evidence on the role of environmental pollutants on gallbladder carcinogenesis. A detailed search of Medline was carried out which revealed only 12 articles. A number of heavy metals like nickel, cadmium, etc. have been implicated; however, the evidence is not robust enough to conclude its association. Role of radiation and pesticides in river water have also been evaluated without any conclusive evidence of its association with gallbladder cancer. Better designed case-control studies or cohort studies looking at exposure are required before it could be accepted as one of the causes of GBC.

Cadmium↗

PubMed1999

The role of antioxidant enzymes in the control of opossum gallbladder motility.

BACKGROUND: Superoxide rapidly oxidizes nitric oxide (NO) to form peroxynitrite, thus terminating the biological activity of NO. The aims of our study were to determine if superoxide alters the motor function of the gallbladder and to localize the antioxidant enzymes in the gallbladder. MATERIALS AND METHODS: Immunostaining and immunoblots were performed and enzyme activities were measured in the gallbladder. In physiologic experiments, force-displacement transducers recorded tension in gallbladder muscle strips. Superoxide was generated by the addition of xanthine with xanthine oxidase, while superoxide radicals were scavenged by the addition of superoxide dismutase (SOD) and catalase. SOD was inhibited by deithyldithiocarbamate. RESULTS: Immunostaining demonstrated superoxide dismutase and catalase immunoreactivity in ganglia situated throughout the smooth muscle. Total superoxide dismutase activity was 115 +/- 12 U/mg. Western blots detected expression of proteins of 19.4 kDa for copper/zinc SOD and 25.0 kDa for manganese SOD. Generation of superoxide increased isometric tension, while pretreatment with SOD prevented the increase in isometric tension induced by superoxide. Inhibition of SOD diminished the EFS-induced off response. CONCLUSIONS: We conclude that superoxide alters gallbladder motor function, and the presence of superoxide scavenging enzymes in enteric plexuses suggests that they may regulate gallbladder neuromuscular function by clearing endogenous superoxide.

Animals↗

PubMed2000

Effect of acalculous cholecystitis on gallbladder neuromuscular transmission and contractility.

BACKGROUND: Impaired smooth muscle contractility is important in the pathophysiology of acalculous cholecystitis. Common bile duct ligation (CBDL) is a model of acalculous cholecystitis, producing acute inflammatory changes and decrease in gallbladder smooth muscle contractility. The aim of this study was to determine whether there is coexistent dysfunction of neural efferent motor pathways of the gallbladder after CBDL. MATERIALS AND METHODS: Gallbladder muscle contractility was studied in vitro in normal, CBDL, and sham-operated guinea pigs. Electric field stimulation (EFS; 2-16 Hz) was used to activate intrinsic nerves and exogenous acetylcholine (ACh) was used to directly stimulate the muscle. H&E-stained slides of muscle strips were scored for inflammatory changes. RESULTS: After CBDL, there was a progressive increase in the inflammation score and decrease in gallbladder muscle contractility to ACh. There was also a progressive decline in EFS-induced contractility when expressed as absolute force or normalized to the maximal muscle contractile response to ACh. The nitric oxide synthase inhibitor l-NNA (10 microM) increased EFS-induced contractions by 50 +/- 25% (P = 0.05) in CBDL animals but had no effect in sham surgical controls. CONCLUSIONS: CBDL with its acute gallbladder inflammation affects gallbladder contractility by two mechanisms: (1) decreased smooth muscle contractility, and (2) decreased neurally mediated contractions. The neurally mediated alterations result from dysfunction of cholinergic excitatory nerves and upregulation of nitric-oxide-mediated inhibition of smooth muscle contractility.

Acetylcholine↗

PubMedDate not supplied

The prokinetic effect of domperidone in gallbladder--not upon dopaminergic receptors.

The mechanism of the contractile effect of domperidone on gallbladder smooth muscle has been investigated by using an in-vivo and an in-vitro model. In the in-vivo part of the study 14 healthy males were administered 20 mg domperidone or two placebo tablets orally and gallbladder emptying was measured by ultrasonography. The reduction in the gallbladder volume was significant compared to the placebo at 45 and 55 min. In the in-vitro part of the study, the gallbladder strips isolated from guinea pigs were field stimulated and 10(-6)-10(-4) M concentrations of dopamine were administered before electrical field stimulation (EFS) was repeated. Dopamine exerted no significant effect upon the contractions obtained by EFS. The effect of dopamine and domperidone under basal conditions were also explored. Under basal conditions, dopamine neither contracted nor relaxed the gallbladder muscle between 10(-6) and 10(-4) M concentrations when added directly to the organ bath. Besides, a significant contraction was observed with 10(-4) M concentration of domperidone whereas 10(-7), 10(-6) and 10(-5) M concentrations exerted no effect. This effect of domperidone was thought to be nonspecific but inhibited by 10(-6) M atropine, 10(-5) M pirenzepine and abolished by 10(-6) M tetrodotoxin. In summary, domperidone produces a modest contraction in human gallbladder. This effect does not seem to occur upon dopaminergic receptors in guinea pig models.

Adult↗

PubMed1995

Experience with laparoscopic double gallbladder removal.

Double gallbladder is a rare congenital anomaly and an encounter with it while performing cholecystectomy laparoscopically is a challenge to the laparoscopic surgeon. A 28-year-old man complaining of epigastric pain was evaluated at Teikyo University Hospital, Mizonokuchi, Japan. There were no abnormal laboratory findings. Ultrasonography revealed an acoustic shadow in each compartment without any inflammatory changes in the gallbladder. No lesions were endoscopically noted in the stomach. CT scan could not demonstrate the anomaly. ERCP revealed a duplication of the gallbladder shadow with a stone in each vesicle and also the confluence of two cystic ducts from both the gallbladders draining into the common bile duct (CBD). Laparoscopic cholecystectomy was performed successfully in this case. This paper presents this particular case because of double gallbladder's rarity in the literature and to emphasize the importance of preoperative cholangiographic evaluation for double gallbladder. The laparoscopic surgeon is given an idea of the meticulous dissection at the "hepatocystic triangle" due to the various other vascular and other congenital anomalies associated with it. An account of the classification of this congenital abnormality and its various types is also discussed here.

Adult↗

PubMed1994

Subcellular characterization of glycoproteins in the principal cells of human gallbladder. A lectin cytochemical study.

Gallbladder mucus is mainly composed of glycoproteins, which seem to play a critical role in cholesterol nucleation during gallstone formation. The biosynthetic pathway and sequential processing as well as the characterization of the oligosaccharide side-chains of human gallbladder secretory glycoproteins have not been completely defined. The aim of the present study is the subcellular characterization of the glycoproteins in the principal cells of human gallbladder. Principal cells of normal human gallbladder were studied by means of a variety of cytochemical techniques, including lectin histochemistry, enzyme and chemical treatments, immunocytochemistry and lectin-gold technology. Fucose, galactose, N-acetylglucosamine, N-acetylgalactosamine and N-acetylneuraminic acid residues were detected in mucous granules, Golgi apparatus and apical membrane of principal cells. Mannose residues were only observed in dense bodies. Oligosaccharide side-chains of the glycoproteins contained in the biliary mucus are synthesized in the Golgi apparatus of the principal cells of the gallbladder epithelium and are also contained in the mucous granules of these cells. Terminal N-acetylneuraminic acid(alpha 2-3)galactose(beta 1-3)N-acetylgalactosamine, N-acetylneuraminic acid(alpha 2-3)galactose(beta 1-4)N-acetylglucosamine and galactose(beta 1-4)N-acetylglucosamine sequences are contained in the oligosaccharide chains of gallbladder mucus glycoproteins. The dense bodies detected in the cytoplasm of the principal cells contained N-linked glycoproteins. Mucin-type O-linked glycoproteins were the main components of the mucous granules although some N-linked chains were also detected.

Carbohydrate Conformation↗

PubMed1990

Effects of cimetropium bromide on gallbladder contraction in response to oral and intraduodenal olive oil.

To evaluate the influence of the stomach and the cholinergic system on gallbladder contraction induced by physiological stimuli, the reduction in gallbladder volume in 7 healthy volunteers has been studied by real-time ultrasonography after the oral and intraduodenal administration of olive oil, preceded by pretreatment with cimetropium bromide or placebo. After an overnight fast, each subject swallowed 50 ml olive oil or it was administered through a naso-duodenal tube in the proximal duodenum. Cimetropium bromide 5 mg or placebo was given intravenously under double-blind control. After the placebo pretreatment, gallbladder contraction was greater and faster after intraduodenal oil than after oral oil. Cimetropium bromide decreased the extent, velocity and duration of gallbladder contraction induced by intraduodenal olive oil but it only reduced the velocity of the contraction induced by oil given orally. It is concluded that in normal human subjects the stomach modulates the extent and velocity of postprandial gallbladder contraction and that anticholinergic agents antagonize the gastric and duodenal phases of the response of the gallbladder to a meal.

Administration, Oral↗

PubMed1989

Percutaneous stone clearance of the gallbladder through an access cholecystostomy. Laparoscopic-guided technique.

A laparoscopic-guided technique of percutaneous gallstone fragmentation/removal has been developed in the pig. The procedure entails the creation of a percutaneous access cholecystostomy. The access tract can be safely dilated after 7 days to F16, thereby allowing the introduction of both the Olympus flexible and the Berci-Shore rigid choledochoscopes. Following endoscopic occlusion of the cystic duct by a biliary balloon catheter, stone fragmentation can be conducted under direct visual control. In this particular study, electrohydraulic lithotripsy was performed of human cholesterol and bile-pigment stones inserted into the gallbladder of 16 pigs. The gallstone debris resulting from lithotripsy was then washed out with saline. Larger residual fragments could easily be extracted with the Dormia basket under visual guidance. There was a significant positive correlation between stone size (r = 0.98) and weight (r = 0.96) and the number of pulses needed to achieve satisfactory stone fragmentation. The gross composition of the stones (predominantly cholesterol or pigment) did not influence the number of pulses required. Electrohydraulic lithotripsy caused an explosion effect (the fragments hit the gallbladder wall), causing submucosal haematoma formation. This, however, was not followed by any untoward effect until sacrifice of the animals 10-16 weeks later. Electrohydraulic shocks delivered to the gallbladder wall itself resulted in larger haematoma formation and breach of the gallbladder mucosa with active bleeding into the gallbladder lumen, but again no instance of gallbladder perforation was encountered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Effect of cold stress on gallbladder contractility in humans.

The effect of cold stress in the form of repeated hand immersion in ice cold water or repeated application to a hand of extremely cold - nitrogen gas, at a temperature of -180 degrees C (93 K), on the emptying of a meal-stimulated gallbladder was examined in seven healthy volunteers of both sexes. The control procedure consisted of repeated application to a hand of air at neutral temperatures (+35 degrees(-)+37 degrees C). Each subject underwent three examinations on separate days, the procedures being applied in random order. Gallbladder volume was measured by means of real-time ultrasonography. Measurements of volumes of the fasted gallbladder were also made on the three study days and gave similar values: 20.3 cm3, SEM 2.7 (control), 22.1 cm3, SEM 2.5 (cryotherapy), and 20.0 cm3, SEM 2.5 (cold immersion), F(2, 12) = 2.47, P greater than 0.1. A significant delaying effect of cold stress on postprandial gallbladder contractility was observed: F(2, 72) = 7.44, P less than 0.005, and F(2, 72) = 4.45, P less than 0.025 for gallbladder volume and ejection fraction, respectively. A significant difference was detected between the local application of cold gas and the control procedure (P less than 0.005) and local cryotherapy and the cold pressor test (P less than 0.05) in the case of the postprandial gallbladder volume, as well as between the local application of cold gas and the control procedure (P less than 0.025) for the ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Laparoscopic cancer surgery. Lessons from gallbladder cancer.

Laparoscopic cholecystectomy (LC) may inhibit the discovery of unsuspected gallbladder cancer, and the effect of LC on the prognosis of gallbladder cancer is unknown. We present two cases of unsuspected gallbladder cancer removed laparoscopically and report the discovery of peritoneal tumor implantation at the umbilical port site 21 days after LC. Although gallbladder carcinoma flow cytometry has been reported to be of prognostic value by Japanese investigators, this technique did not distinguish herein between an invasive adenocarcinoma and carcinoma in situ. A cellular doubling time of 56 h was calculated from one tumor. When unsuspected invasive gallbladder cancer is found after LC, laparoscopic port sites should be inspected at reoperation and, at a minimum, the port site through which the gallbladder was removed should be widely excised. This demonstration of cancer recurrence in laparoscopic port sites may limit the application of laparoscopy to elective cancer resection.

Adenocarcinoma↗

PubMed1995

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 super-saturated with cholesterol. In the present study, using an enzyme-linked immunosorbent assay of apolipoprotein A1, we determined the content of apolipoprotein A1 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 micrograms/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 micrograms/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.

Apolipoprotein A-I↗