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At least 19 recordsLinked to original sources
PubMed2000

Biliary lipid composition in patients with cholesterol and pigment gallstones and gallstone-free subjects: deoxycholic acid does not contribute to formation of cholesterol gallstones.

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.

Adolescent↗
PubMed1987

Dissolution of cholesterol gallstones in vitro. Gallstone matrix content and diameter, not cholesterol content, predict gallstone dissolution in monooctanoin.

The goal of this study was to identify the structural and compositional features of human gallstones that influence in vitro gallstone dissolution in the cholesterol solvent monooctanoin. Gallstones were obtained from 86 consecutive patients who had at least three morphologically similar stones. One stone from each patient was dissolved in ethanol/ether to determine cholesterol and matrix composition. The remaining two matched stones were dissolved in either monooctanoin plus ethanol (n = 86) or monooctanoin plus 2-mercaptoethanol (n = 86). The thiol reducing agent 2-mercaptoethanol has been previously shown to solubilize the isolated gallstone matrix and to accelerate the dissolution of intact, small cholesterol stones. Stone matrix content and initial diameter had the most significant predictive value for stone dissolution (p less than 0.0001 for each), whereas cholesterol content had no predictive value (p = 0.558). Stones incubated in monooctanoin containing 2-mercaptoethanol dissolved more rapidly than those incubated in monooctanoin plus ethanol (16.7% of initial weight per day vs. 13.8% of initial weight per day, p less than 0.0001). Matrix content correlated significantly with the difference in dissolution rate between stones dissolved in monooctanoin plus ethanol or monooctanoin plus 2-mercaptoethanol (p less than 0.0001). These data indicate that the matrix content of human cholesterol gallstones significantly inhibits in vitro stone dissolution in the cholesterol solvent monooctanoin. This finding may be relevant to the clinical dissolution of gallstones.

Caprylates↗
PubMed2004

Bile acid synthesis is increased in Chilean Hispanics with gallstones and in gallstone high-risk Mapuche Indians.

BACKGROUND & AIMS: Gallstone disease is an important, costly health-care problem in Western societies. It is still unclear whether hepatic lipid regulatory enzymes play primary or secondary roles in gallstone formation. In this study, the aim was to investigate whether the synthesis of bile acids and cholesterol is increased in gallstone disease and to test whether such a metabolic change, if present, might occur before gallstone formation. METHODS: A total of 125 Chilean Hispanic women (80 without gallstones and 45 with gallstones) matched for age and body mass index were investigated, along with 40 Chilean Mapuche Indian women (20 without gallstones and 20 with gallstones), a population group in which the prevalence for gallstone disease is very high. Fasting blood plasma samples were assayed for 7 alpha-hydroxy-4-cholesten-3-one and lathosterol, 2 strong indicators for hepatic bile acid and body cholesterol synthesis, respectively. RESULTS: Plasma 7 alpha-hydroxy-4-cholesten-3-one levels, corrected for plasma cholesterol, were significantly increased by 50% in Hispanic women with gallstones as compared with gallstone-free Hispanics (P < 0.006). As compared with Hispanic women without gallstones, plasma 7 alpha-hydroxy-4-cholesten-3-one levels were increased by > or =100% (P < 0.002) in Mapuche Indian women, independently of whether gallstones were present. Plasma lathosterol, corrected for plasma cholesterol, was significantly increased by 22% in Hispanic women with gallstones and in Mapuche Indian women compared with Hispanic women. CONCLUSIONS: The results indicate that the synthesis of bile acids and cholesterol is induced in gallstone disease and precedes gallstone development. These inductions presumably occur as a response to an increased intestinal loss of bile acids.

Adult↗
PubMed1990

Gallbladder motility in cholesterol gallstone disease. Effect of ursodeoxycholic acid administration and gallstone dissolution.

Gallbladder motility was evaluated by ultrasonography in 75 cholesterol gallstone patients and in 77 matched control subjects. All 75 gallstone patients were candidates for oral bile acid therapy (radiolucent gallstones, less than 2 cm in diameter, in well-opacified gallbladder), and 38 of them were also studied during ursodeoxycholic acid administration. An additional 20 gallstone patients were studied 1 year after confirmed gallstone dissolution with oral bile acids. Gallstone patients showed significantly greater fasting and residual volumes, a decreased percent of gallbladder emptying, but a similar absolute emptying and emptying rate compared with the control subjects. Greater fasting volumes and reduced percents of gallbladder emptying were also found in gallstone-free patients who achieved complete dissolution with oral bile acids. After ursodeoxycholic acid administration, fasting gallbladder volumes were greater, and percents of gallbladder emptying were further decreased than in untreated gallstone patients. In conclusion, greater fasting volumes, and not reduced gallbladder contractility, account for the defective gallbladder function in radiolucent (cholesterol-rich) gallstone patients. This condition is likely to precede, and possibly to promote, gallstone formation because it persists after gallstone dissolution. Ursodeoxycholic acid administration worsens the defect observed in gallstone patients. This finding also suggests, although indirectly, that the expected normalization of cholesterol saturation during oral bile acid administration is not paralleled by an improvement in gallbladder function.

Adolescent↗
PubMed2000

Differential effect of prostaglandins on gallstone-free and gallstone-containing human gallbladder.

Nonsteroidal antiinflammatory drugs, inhibitors of prostaglandin synthesis, have different effects on gallbladder contractility in normal and diseased human gallbladders in vivo. We investigated this differential effect by comparing the effects of prostaglandins PGE2 and PGF2alpha, the thromboxane A2 mimetic U46619, and PGI2 on in vitro contractility in gallstone-free and gallstone-containing human gallbladders. Isometric tension was measured in gallbladder muscle strips mounted in organ baths. EC50 was calculated for each agonist. The rank order of potency in gallstone-free gallbladders was PGE2 > CCK > U46619 > PGF2alpha and in gallstone-containing gallbladders was U46619 > PGE2 > CCK > PGF2alpha. PGI2 produced contraction of gallstone-free gallbladder and relaxation of gallstone-containing gallbladder in the basal state. Further, PGI2 produced no relaxation in gallstone-free muscle strips precontracted with CCK, but significant relaxation in CCK precontracted gallstone-containing strips. PGE2, PGF2alpha, and U46619 are potent contractors of gallstone-free and gallstone-containing gallbladders, whereas PGI2 relaxes only gallstone-containing gallbladders. Since gallbladders containing cholesterol-supersaturated bile produce increased PGI2, this PGI2-induced relaxation may be a determinant of the impaired gallbladder motility of gallstone disease.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMedDate not supplied

Relation between the risk of gallstone pancreatitis and characteristics of gallstone in Korea.

BACKGROUND/AIMS: Pancreatitis is a serious complication of patients with gallstones. However, risk factors of gallstone pancreatitis were unpredictable until recently. In Korea, characteristics of gallstones are different from Western countries. The present study was designed to determine differences in the risk of gallstone pancreatitis and characteristics of gallstones in Korean patients. METHODOLOGY: Clinical data were collected on patients undergoing laparoscopic cholecystectomy. The physical characteristics of gallstones recovered at surgery were also recorded. Patients with gallstone pancreatitis were compared with patients who had uncomplicated biliary pain. RESULTS: In a logistic regression model, acute gallstone pancreatitis was associated with a stone diameter of less than 5 mm (odds ratio: 3.3695; P = 0.0352) and with stone number of more than 20 (odds ratio: 3.8686; P = 0.0361). No other variable, including pigment stone, age, and sex, remained statistically significant in the adjusted analysis (P > 0.05). CONCLUSIONS: Patients with at least 1 gallstone smaller than 5 mm in diameter and stone number more than 20 each have a more than 3-fold increased risk of presenting with acute gallstone pancreatitis. The composition of gallstones, especially pigment stones, was not an important risk factor in gallstone pancreatitis in Korean patients with stones having a different composition than those from Western countries.

Acute Disease↗
PubMed2006

Predictors of gallstone composition in 1025 symptomatic gallstones from Northern Germany.

BACKGROUND: Gallstones represent a prevalent and costly health problem. The changing epidemiology and the emerging non-surgical interventions for gallstone disease necessitate the definition of target populations for future therapies. This study aimed to define patterns of gallstone composition and identify demographic predictors of gallstone composition in a large sample of symptomatic gallstones from Northern Germany. METHODS: One thousand and seventy-four post-cholecystectomy gallstone specimens were obtained. Demographic and clinical information was provided by questionnaire (N = 1025 independent individuals with complete information). Two samples from each gallstone were analyzed using Fourier transformed infrared spectrometry. RESULTS: The most prevalent substance was cholesterol, which was detected in 95.0% of gallstone specimens. Bilirubin and bilirubinate were present in 30.0% and calcium was detected in 10.0% of the spectra. Ninety-two percent of measurements from the same stone yielded the same "main" substances, indicating a homogenous stone composition in most cases. Female sex and higher body mass index (BMI) were associated with the presence of cholesterol as a main substance in the gallstones (p < 0.001). CONCLUSION: The changing epidemiology of gallstone disease is reflected by a marked shift in stone composition: Only two percent of stones in this study were pigment stones as compared to 91% percent of stones containing cholesterol as a main substance. Obese individuals from Germany with a BMI > 30 kg/m2 have in 95% cholesterol-dominant gallstones and represent a potential target population for non-surgical interventions for the prevention or treatment of cholesterol stones.

Age Factors↗
PubMed2000

Risk factors for the development of gallstone recurrence following medical dissolution. The British-Italian Gallstone Study Group.

OBJECTIVE: To assess risk factors for gallstone recurrence following non-surgical treatment. DESIGN: A prospective follow-up of a multicentre cohort of post-dissolution gallstone patients. SETTING: Six gastroenterology units in the UK and Italy. PARTICIPANTS: One hundred and sixty-three patients with confirmed gallstone dissolution following non-surgical therapy (bile acids or lithotripsy plus bile acids), followed up by ultrasound scan and clinical assessment at 6-monthly intervals for up to 6 years (median, 25 months; range, 6-70 months). OUTCOME MEASURES: Subject-related variables (sex, age, height, weight, body mass index), gallstone-related variables (number, diameter, presence of symptoms, months to complete stone clearance), treatment modalities (bile acid therapy, extracorporeal shock wave lithotripsy) and follow-up related variables (weight change, use of non-steroidal anti-inflammatory agents, statins, pregnancies and/or use of oestrogens) were assessed by univariate and multivariate analysis as putative risk factors for gallstone recurrence. RESULTS: Forty-five gallstone recurrences were observed during the follow-up period. Multiple primary gallstones and length of time to achieve gallstone dissolution were the only variables associated with a significant increase in the recurrence rate. Appearance of biliary sludge during follow-up was also significantly related to development of gallstone recurrence. Use of statins or non-steroidal anti-inflammatory agents did not confer protection against recurrence. CONCLUSIONS: Patients with primary single stones are the best candidates for non-surgical treatment of gallstones, because of a low risk of gallstone recurrence. The positive association of recurrence with biliary sludge formation and time to dissolution of primary stones may provide indirect confirmation for the role of impaired gallbladder motility in the pathogenesis of this condition.

Adolescent↗
PubMed1996

Lysosomal enzyme activities in gallbladder mucosa of gallstone-free subjects and patients with gallstones.

BACKGROUND/AIMS: Gallstone patients have a reduced cellular lysosome content in the gallbladder mucosa cells compared with gallstone-free subjects. The purpose of the study was to further evaluate the possible role of lysosomes in the pathogenesis of cholesterol gallstone formation in humans. METHODS: Lysosomal enzyme activities were assayed in gallbladder mucosa and for comparison in liver specimens of 19 gallstone-free subjects and 24 gallstone patients undergoing cholecystectomy. RESULTS: Gallstone patients had 25-50% lower activities of the lysosomal proteases cathepsin B, D and L in their gallbladder mucosa compared with gallstone-free subjects. The activity of acid phosphatase also tended to be decreased in gallstone patients. The liver lysosomal enzyme activities were not significantly different between the two groups. CONCLUSIONS: The results show that gallstone patients have diminished lysosomal enzyme activities in the gallbladder mucosa, a finding which may be related to decreased intracellular degradation of proteins and/or mucin in the mucosal cells. This may lead to a higher concentration of mucin in gallbladder bile and thus an increased risk of precipitation of cholesterol crystals and gallstone formation.

Acid Phosphatase↗
PubMed1995

Biliary alpha 1-acid glycoprotein concentrations in gallstone-free controls and in patients with multiple or solitary cholesterol gallstones.

We recently identified a promoting glycoprotein in the concanavalin A-bound fraction of gallbladder bile as a biliary form of alpha 1-glycoprotein (AAG). The concentration of biliary AAG appears to exert an important promoting effect on the speed of cholesterol nucleation in many patients with cholesterol gallstone disease. In the current study, we provide information about the biliary concentration of AAG as well as the amount and comparative potency of its subfractions in patients with and without cholesterol gallstone disease. The amount of total biliary AAG and the amounts of its different isoforms separated by concanavalin A affinity chromatography were measured by ELISA. Estimates of absolute concentrations of AAG for each sample were normalized to the sample total protein content to give relative AAG values. The promoting activity (potency) of immunopurified biliary AAG from gallstone patients and gallstone-free controls on cholesterol crystallization was compared by a crystal growth assay. The mean absolute concentration of AAG in gallstone-free controls was not significantly different from multiple stone patients. The relative concentration of AAG (micrograms per milligram total protein) was significantly increased in patients with multiple stones when compared to controls (P < 0.05), and both the absolute and relative concentrations of AAG (micrograms per milligram bile), were three- and to five fold higher in a number of these patients. The functional activity and distribution of AAG in different subfractions was similar in gallstone patients and gallstone-free controls. The relative concentration of biliary AAG is significantly greater in cholesterol gallstone patients with multiple stones than in gallstone-free controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile↗
PubMed1995

High familial prevalence of gallstones in the first-degree relatives of gallstone patients.

Limited information is available on the prevalence of gallstones in the first-degree relatives of gallstone patients. Three groups of subjects were studied by real-time ultrasound examination: group A, 105 index gallstone patients (male/female; 20:85); group B, 330 first-degree relatives of index patients; group C, matched controls for group A (n = 105) and group B (n = 330) subjects. Dietary, anthropometric, and biochemical investigations were carried out. In 39 of 105 (37%) index cases, one or more additional family members had gallstones (positive-index case). The positive-index cases were younger than the remaining index cases (mean age, 33.1 +/- 14 vs. 44.5 +/- 13.1 years; P < .05). Fifty-one of 330 (15.5%) first-degree relatives had gallstones, nearly four and a half times (95% confidence interval [CI], 2.4 to 8.5) more often than in the matched control population (12 of 330 [3.6%]). Thirty-three of 51 (65%) positive relatives were women; mother (37.3%), sister (17.6%) or daughters (10%) to the index patients. There was no difference in the diet, physical activity, and serum lipid profile between the positive index patients and the remaining gallstone patients and positive relatives and their controls. Our results show that there is a strong familial predisposition for gallstone formation. Female relatives of young gallstone patients should be routinely screened for gallstones.

Adult↗
PubMed2006

Gallstones and gallbladder cancer-volume and weight of gallstones are associated with gallbladder cancer: a case-control study.

BACKGROUND: Gallstones are considered the most important risk factor for gallbladder cancer. AIM: To identify differences in the number, weight, volume, and density of gallstones associated with chronic cholecystitis (CC), gallbladder dysplasia (GD), and gallbladder cancer (GBC). METHODS: A total of 125 cases were selected, of which 93 had gallstones associated with GBC and 31 had gallstones associated with GD. The controls were those with CC, matched by sex and age. The number, weight, volume, and density of these gallstones were examined in order to determine differences and relative cancer risk. RESULTS: Number: Multiple gallstones were present in over 76% of cases (GBC and GD) and controls (P = ns). The average number of multiple stones was 21 in GBC versus 14 in controls (P < 0.01). Weight: The average weight of the gallstones was 9.6 g in GBC versus 6.0 g in controls (P = 0.0004). The average weight in multiple stones over 10 g had strong association with GBC (P = 0.0006). Volume: The average volume was 11.7 and 6.48 ml in GBC and controls (P = 0.0002). Average volumes of 6, 8, and 10 ml had a relative cancer risk of 5, 7, and 11 times, respectively. Size: No differences were shown between GBC, GD, and controls. CONCLUSIONS: The volume of gallstones associated with other risk factors of GBC may be helpful in prioritizing cholecystectomies in symptomatic patients.

Analysis of Variance↗
PubMed1991

Replacement of cholesterol gallstones by murideoxycholyl taurine gallstones in prairie dogs fed murideoxycholic acid.

The effect of two hydrophilic bile acids, murideoxycholic acid (3 alpha,6 beta-dihydroxy-5 beta-cholanoic acid) and ursodeoxycholic acid, on cholesterol and bile acid metabolism and hepatic pathology and gallstone composition was studied in the prairie dog. Cholesterol gallstones were induced by feeding a diet containing 1.2% cholesterol for 75 days. The animals were divided into six groups, and gallstone regression was studied as follows: groups 2 and 5, chow plus 0.2% cholesterol; groups 3 and 6, chow plus 0.2% cholesterol plus 0.15% ursodeoxycholic acid; groups 4 and 7, chow plus 0.2% cholesterol plus 0.15% murideoxycholic acid. Animals in groups 2 to 4 were killed after an additional 6 wk; animals in groups 5 to 7 were killed after an additional 12 wk. Gallstone dissolution did not occur in any group. The gallstones in groups 2, 3, 5 and 6 were typical cholesterol aggregates, as determined by polarized light microscopy and Fourier transform infrared spectrometry. The gallstones of the murideoxycholic acid group were large, solitary, dark stones that appeared radiopaque under 22 kVp x-ray examination. Scanning electron microscopy showed that in these stones the cholesterol crystals had been replaced by an amorphous material, both within the stone and on the stone surface. Chemical analysis indicated that at the end of 12 wk the calcium/sodium salt of the taurine conjugate of murideoxycholic acid (murideoxycholyl taurine) comprised 70% of the stones; protein, cholesterol and small amounts of other bile salts were also present. In vitro studies confirmed the insolubility of the sodium and calcium salts of murideoxycholyl taurine. These studies indicate that the hydrophilic bile acids, murideoxycholic acid and ursodeoxycholic acid, did not achieve gallstone dissolution under the conditions used. In the animals fed murideoxycholic acid, an insoluble calcium salt of murideoxycholyl taurine replaced cholesterol as the major constituent of gallbladder stones. This is the first example of an insoluble dihydroxy taurine-conjugated bile acid; administration of the unconjugated bile acid induced precipitation of a kind of gallstone not previously reported. The final result was transformation of cholesterol stones to bile salt stones.

Animals↗
PubMed2001

Chromosomal organization of candidate genes involved in cholesterol gallstone formation: a murine gallstone map.

Epidemiologic and family studies indicate that cholesterol gallstone formation is in part genetically determined. The major contribution to our current understanding of gallstone genes derives from animal studies, particularly cross-breeding experiments in inbred mouse strains that differ in genetic susceptibility to cholesterol gallstone formation (quantitative trait loci mapping). In this review we summarize how the combined use of genomic strategies and phenotypic studies in inbred mice has proven to be a powerful means of dissecting the complex pathophysiology of this common disease. We present a "gallstone map" for the mouse, consisting of all genetic loci that have been identified to confer gallstone susceptibility as well as putative candidate genes. Translation of the genetic loci and genes between mouse and human predicts chromosomal regions in the human genome that are likely to harbor gallstone genes. Both the number and the precise understanding of gallstone genes are expected to further increase with rapid progress of the genome projects, and multiple new targets for early diagnosis and prevention of gallstone disease should become possible.

Animals↗
PubMedDate not supplied

Polarizing microscopy of partially dissolved gallstone powder: a simple technique for studying gallstone composition.

A quick and reliable method for estimating the proportion of constituents of a stone may be useful in determining the prevalence of chemical type of gallstones in different geographic areas or ethnic groups. Chemical and infrared spectroscopy estimation facilities are not commonly available in many parts of the world and visual inspection may not be reliable for scientific purposes. To investigate whether identification of microcrystalline solids in partially dissolved stone powder could accurately predict the chemical nature of the gallstone we undertook a blind study on 40 samples of gallstones and compared our results with those of visual inspection and quantitative infrared spectroscopy. There were 29 cholesterol stones (mean cholesterol 83.4 +/- 7.5%), six intermediate cholesterol stones (mean cholesterol 48.0 +/- 21.2%) and five pigment stones (mean cholesterol 14.3 +/- 4.3%) as determined by quantitative infrared spectroscopy. Microscopic examination of partially dissolved gallstone powder in ethanol correctly identified all 29 cholesterol gallstones (sensitivity 100%, specificity 92%), four of six intermediate cholesterol stones (sensitivity 67%, specificity 100%) and all five pigment stones (sensitivity 100%, specificity 97%). It also detected microspheroliths of calcium carbonate in 14 of 16 calcium carbonate containing gallstones (sensitivity 88%, specificity 100%). The chemical grouping of stones on the basis of microscopic examination was correct in 37 (93%) of 40 samples and was especially useful in identifying 'intermediate' cholesterol stones which cannot be recognized by visual inspection. Thus microscopic examination of powdered gallstones appears to be a simple and reliable method of determining gallstone composition.

Bilirubin↗
PubMed2002

Complications of gallstone disease: Mirizzi syndrome, cholecystocholedochal fistula, and gallstone ileus.

Gallstone is a common disease with a 10% prevalence in the United States and Western Europe. However, it is only symptomatic in 20-30% of patients, with biliary pain "colic" being the most common symptom. Complications of asymptomatic gallstone disease are generally rare, with an incidence of <1 %/yr. The most common complications of gallstone disease are acute cholecystitis, acute pancreatitis, ascending cholangitis, and gangrenous gallbladder. Less frequent complications include Mirizzi syndrome, cholecystocholedochal fistula, and gallstone ileus. Mirizzi syndrome and cholecystocholedochal fistula are two manifestations of the same process that starts with impaction of a gallstone in the gallbladder neck that results in obstruction of the bile duct, causing jaundice. The gallstone may erode into the bile duct, causing cholecystocholedochal fistula. Gallstone ileus refers to small bowel obstruction resulting from the impaction of one or more gallstones after they have migrated through a cholecystoenteric fistula. An accurate diagnosis is essential to the management and prevention of further complications. A variety of imaging and endoscopic modalities are used to make the diagnosis once the condition is suspected clinically. Treatment should be tailored to each individual patient. Management choices include ERCP, lithotripsy (endoscopic or extracorporeal), and surgery. Prognosis is frequently related to early recognition, management of any comorbid conditions, and careful selection of treatment modalities.

Biliary Fistula↗
PubMed1985

Identification of gallbladder mucin-bilirubin complex in human cholesterol gallstone matrix. Effects of reducing agents on in vitro dissolution of matrix and intact gallstones.

The goals of this study were to isolate and characterize the nonlipid matrix of human cholesterol gallstones. The lipid portion of gallstones was dissolved in ethanol/ether, leaving an insoluble, granular, brown-black matrix that constituted 12.5% of solitary large stones and 3.5% of multiple small stones. The matrix was partially solubilized by sonication and studied by exclusion gel chromatography and density gradient ultracentrifugation. On Sepharose 2B column chromatography, bile pigment eluted with glycoprotein in the void volume, suggesting the presence of a high molecular weight complex (Mr greater than 2 X 10(6)). The identity of mucin in this complex was confirmed by its typical buoyant density during ultracentrifugation. The major bile pigments in the matrix were identified as bilirubin (84%) and bilirubin monoglucuronide (15%) by thin-layer chromatography. Because of their ability to solubilize mucin-type glycoproteins, we tested the ability of the reducing agents 2-mercaptoethanol (2ME) and N-acetylcysteine (NAcCys) to solubilize gallstone matrix. Both reducing agents caused a two- to threefold enhancement of matrix dissolution after 4 d compared to aqueous buffer alone (P less than 0.01). Sepharose 2B chromatography revealed that 2ME released a high molecular weight mucin-bilirubin complex as well as unbound pigment from the insoluble matrix. We also tested the effect of reducing agents on dissolution of matched cholesterol gallstones by monooctanoin, a cholesterol solvent. Both 2ME and NAcCys significantly accelerated gallstone dissolution in monooctanoin. Matched human cholesterol stones (n = 10) incubated for 4 d in monooctanoin plus either 2ME or NAcCys (1 M final concentration) weighed approximately half as much (P less than 0.01 for each) as stones incubated in monooctanoin alone. This study describes, for the first time, the isolation of a bilirubin-mucin complex in the insoluble matrix of human cholesterol gallstones. The ability of reducing agents to dissolve the matrix and thereby accelerate gallstone dissolution by monooctanoin in vitro may be relevant to gallstone dissolution in humans.

Acetylcysteine↗
PubMed1987

Radiologic appearance of gallstones and its relationship with biliary symptoms and awareness of having gallstones. Observations during epidemiological studies. Rome Group for the Epidemiology and Prevention of Cholelithiasis (GREPCO).

In the course of two cross-sectional epidemiological surveys carried out by the Rome Group for Epidemiology and Prevention of Cholelithiasis (GREPCO), cholecystography was performed in 82 of 126 subjects identified by means of ultrasonography as having gallstones. In four subjects gallstones were not detected by cholecystography. The x-ray characteristics of the gallbladder and gallstones of the remaining 78 subjects were related to age, sex, presence of biliary symptoms in the five years prior to the study, and awareness of having gallstones. Twenty-three of the 78 gallstone subjects (29.5%) showed a nonvisualized gallbladder. Among the 55 subjects with visualized gallbladder, 16 (29.1%) and 28 (50.9%) showed radiopaque and solitary stones, respectively. The mean diameter of the largest stone was 19.7 mm +/- 11.2 (SD). Age was related inversely to the number of stones. X-ray characteristics of gallstones did not differ between men and women. Presence of biliary symptoms in the five years prior to the study or awareness of having gallstones were not related to any radiologic feature, either in univariate or multivariate statistical analysis which included age, sex, weight, and height as possible confounding variables. Nineteen (24.3%) of the 78 subjects showed gallstones which would have been suitable for medical therapy with bile acids (ie, radiolucent, with a diameter of less than 20 mm, and in a visualized gallbladder).

Adult↗