OBJECTIVETo evaluate the pro-nucleating activity in 33.5 x 10(3) vesicular protein.

METHODSThe model biles were established according Kibe and Zhu. The pro-nucleating activity of 33.5 x 10(3) vesicular protein were examined by polarized light microscopy. The protein and its enzymatic deglycosylation and proteolysis fractions nucleation promoting activity were detected by cholesterol crystal growth assay.

RESULTS33.5 x 10(3) vesicular protein displayed apparent potency of pro-nucleation with activity of 0.310, and derived crystal growth curve indices It, Ig, Ic were presented as 0.57, 1.52, 1.63 respectively, but after treated by N-glycanase enzyme and pronase, no promoting activity were found.

CONCLUSIONThe 33.5 x 10(3) vesicular protein may be involved in the nucleation process of gallstone formation, which is regulated by its peptide and sugar chain.

Bile ; metabolism ; Cholelithiasis ; physiopathology ; Cholesterol ; metabolism ; Humans ; Macromolecular Substances ; Microscopy ; Models, Biological ; Protein Transport ; Proteins ; metabolism

OBJECTIVETo investigate differences between hepatic and biliary lipid metabolism and secretion of genetically gallstone-susceptible (C57L) and resistant (AKR) mice and the mechanism of cholesterol gallstone formation.

METHODSThe inbred C57L and AKR mice were fed a lithogenic diet containing 15% fat, 1.25% cholesterol and 0.5% cholic acid for four weeks. Hepatic cholesterol content and secretion rates of biliary lipids, as well as phenotypes of the liver and gallbladder were determined and examined before and after the feeding of the lithogenic diet.

RESULTSBoth before and after ingestion of the lithogenic diet, hepatic secretion rates of all biliary lipids in C57L mice were markedly higher than that of AKR mice (P < 0.05, P < 0.01, respectively), whereas hepatic cholesterol contents of C57L mice were significantly lower than that of AKR mice (P < 0.05). Furthermore, after consumption of the lithogenic diet, the increase in hepatic secretion rate of biliary cholesterol in C57L mice was significantly higher than that in AKR mice (P < 0.01). Cholesterol gallstones formed in C57L mice and fatty livers developed in AKR mice.

CONCLUSIONSBiliary cholesterol hypersecretion is the key pathophysiological defect of gallstone formation, lith genes have effects on biliary cholesterol hypersecretion and susceptibility to cholesterol gallstone formation in C57L mice. Lithogenic bile is formed at the canalicular membrane and precedes the development of cholesterol gallstones. It is most likely that cholesterol and bile acid hyposecretion make the AKR strain susceptible to the development of fatty livers and resistant to gallstone formation.

Animals ; Bile ; metabolism ; Cholelithiasis ; genetics ; metabolism ; Cholesterol ; analysis ; metabolism ; Fatty Liver ; etiology ; Genetic Predisposition to Disease ; Lipid Metabolism ; Liver ; metabolism ; Male ; Mice ; Mice, Inbred AKR ; Mice, Inbred C57BL

BACKGROUND/AIMS: Gallbladder (GB) mucin is one of the key factors in the gallstone formation. However, there is little information about the diversity of mucin secretion according to the stone composition. Epidermal growth factor receptor (EGFR) functions in proliferation including mucin secreting goblet cell hyperplasia. We compared the expressions of MUC3, MUC5AC, MUC6 and EGFR in the GB epithelium with cholesterol gallstones (GB-chol) group and pigment gallstones (GB-pig group). METHODS: GBs from elective laparoscopic cholecystectomy for the gallstone disease were studied. Stone composition was analyzed by the spectrophotometer. Immunohistochemical stain was performed using each monoclonal antibody. The percentage of stained proportion was scored by the NIH image program and the results were compared between both groups. RESULTS: Total 20 patients were enrolled (10 patients with cholesterol gallstones, 10 patients with pigment gallstones). The percentages of stained proportion for MUC3, MUC5AC, and MUC6 were 42+/-27%, 31+/-15%, and 17+/-9%, respectively in GB-chol group and 32+/-22%, 33+/-23%, and 15+/-10%, respectively in GB-pig group (p>0.05). The expression of EGFR was 50% (5/10) in the GB-chol group and 80% (8/10) in the GB-pig group respectively. CONCLUSIONS: There was no difference in the expressions of MUC3, MUC5AC, and MUC6 between the two groups. Further studies are needed to elucidate the role of EGFR in the gallstore formation.
Bile Pigments/analysis ; Cholelithiasis/chemistry/*metabolism ; Cholesterol/analysis ; Epithelium/metabolism ; Gallbladder/*metabolism ; Humans ; Immunohistochemistry ; Mucin 5AC ; Mucin-3 ; Mucin-6 ; Mucins/*analysis ; Receptor, Epidermal Growth Factor/*analysis

OBJECTIVETo explore the relationship of bacteria identified in cholesterol gallstones and gallstone formation.

METHODSObserve the bacteria activity in model bile and the influence of bacteria on the cholesterol nucleation time (NT).

RESULTS(1) Model bile were suitable for the growth of E. coli, Pseudomonas aeruginosa, staphylococcus aureus, enterococcus faecalis, clostridium difficile and Clostridium. Propionibacterium acne grew weakly and the growth of Bacteroides fragilis was restrained in model bile. (2) Only pseudomonas aeruginosa and enTerococcus faecalis could ly shorten the cholesterol nucleation time. (3) With pseudomonas aeruginosa or enTerococcus faecalis added in model bile, the formation of cholesterol crystals presented a progressive course of evolution.

CONCLUSIONSPseudomonas aeruginosa and enterococcus faecalis, not propionibacterium acne, have pro-nucleating ability in model bile.

Bile ; metabolism ; microbiology ; Cholelithiasis ; microbiology ; Cholesterol ; metabolism ; Crystallization ; Enterococcus faecalis ; growth & development ; Models, Biological ; Propionibacterium acnes ; growth & development ; Pseudomonas aeruginosa ; growth & development

Animals ; Bile Acids and Salts ; metabolism ; Cholelithiasis ; physiopathology ; Cholesterol ; metabolism ; Cholesterol, Dietary ; administration & dosage ; Feces ; chemistry ; Female ; Gallbladder ; physiopathology ; Guinea Pigs ; Myoelectric Complex, Migrating

OBJECTIVETo explore the metabolism-related risk factors of cholelithiasis among residents in Beijing.

METHODSThe clinical data including previous disease history, findings of physical examination, and results of cholecystosonography of 2270 patients with cholelithiasis identified in the Health Screening Center of Peking Union Medical College Hospital between August 2007 and August 2010 were retrospectively reviewed (the case group). Meanwhile, 4336 healthy individuals during the same period were randomly chosen as the control group.

RESULTSTotal cholesterol, triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, body mass index, and systolic blood pressure were positively correlated with the incidence of cholelithiasis (P < 0.05), while high-density lipoprotein cholesterol was negatively correlated (P < 0.05). Diastolic blood pressure showed no association with cholelithiasis (P > 0.05).

CONCLUSIONCholelithiasis is resulted from multiple factors including elevated blood lipids, blood glucose, and systolic blood pressure among residents in Beijing.

Adult ; Aged ; Blood Glucose ; Blood Pressure ; Case-Control Studies ; China ; epidemiology ; Cholelithiasis ; epidemiology ; metabolism ; Female ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Risk Factors

The etiology of biliary tract cancer is obscure, but there are evidences that bile acid plays a role in carcinogenesis. To find the association between biliary tract cancer and bile acid, this study compared the bile acid concentration and composition among patients with biliary cancer, biliary tract stones, and no biliary disease. Bile was compared among patients with biliary tract cancer (n = 26), biliary tract stones (n = 29), and disease free controls (n = 9). Samples were obtained by percutaneous transhepatic biliary drainage, endoscopic nasobiliary drainage, or gallbladder puncture, and analyzed for cholic, deoxycholic, chenodeoxycholic, lithocholic, and ursodeoxycholic acid composition. Total bile acid concentration was lower in the cancer group than the biliary stone and control groups; the proportions of deoxycholic (2.2% vs. 10.2% and 23.6%, p < 0.001 and p < 0.001, respectively) and lithocholic acid (0.3% vs. 0.6% and 1.0%, p = 0.065 and p < 0.001, respectively) were also lower. This result was similar when disease site was limited to bile duct or gallbladder. Analysis of cases with bilirubin < or = 2.0 mg/dL also showed lower total bile acid concentration and deoxycholic acid composition in the cancer group compared to controls (5.7% vs. 23.6%, p = 0.003). Although the presence of bile duct obstruction explains some of the difference in total concentration and composition of bile acid, there are other contributing mechanisms. We suspect the alteration of bile acid transport might decrease bile acid excretion and cause the accumulation of carcinogenic bile acid in bile duct epithelium.
Tumor Markers, Biological/analysis ; Middle Aged ; Male ; Humans ; Gallbladder Neoplasms/metabolism ; Female ; Cholic Acids/*analysis/metabolism ; Cholelithiasis/metabolism ; Biliary Tract Neoplasms/*chemistry/metabolism ; Aged, 80 and over ; Aged ; Adult ; Adolescent

The etiology of biliary tract cancer is obscure, but there are evidences that bile acid plays a role in carcinogenesis. To find the association between biliary tract cancer and bile acid, this study compared the bile acid concentration and composition among patients with biliary cancer, biliary tract stones, and no biliary disease. Bile was compared among patients with biliary tract cancer (n = 26), biliary tract stones (n = 29), and disease free controls (n = 9). Samples were obtained by percutaneous transhepatic biliary drainage, endoscopic nasobiliary drainage, or gallbladder puncture, and analyzed for cholic, deoxycholic, chenodeoxycholic, lithocholic, and ursodeoxycholic acid composition. Total bile acid concentration was lower in the cancer group than the biliary stone and control groups; the proportions of deoxycholic (2.2% vs. 10.2% and 23.6%, p < 0.001 and p < 0.001, respectively) and lithocholic acid (0.3% vs. 0.6% and 1.0%, p = 0.065 and p < 0.001, respectively) were also lower. This result was similar when disease site was limited to bile duct or gallbladder. Analysis of cases with bilirubin < or = 2.0 mg/dL also showed lower total bile acid concentration and deoxycholic acid composition in the cancer group compared to controls (5.7% vs. 23.6%, p = 0.003). Although the presence of bile duct obstruction explains some of the difference in total concentration and composition of bile acid, there are other contributing mechanisms. We suspect the alteration of bile acid transport might decrease bile acid excretion and cause the accumulation of carcinogenic bile acid in bile duct epithelium.
Tumor Markers, Biological/analysis ; Middle Aged ; Male ; Humans ; Gallbladder Neoplasms/metabolism ; Female ; Cholic Acids/*analysis/metabolism ; Cholelithiasis/metabolism ; Biliary Tract Neoplasms/*chemistry/metabolism ; Aged, 80 and over ; Aged ; Adult ; Adolescent

This study was designed to investigate the effect of cholestyramine on the formation of pigment gallstones in high carbohydrate diet-fed hamsters and whether that effect occurred because of cholecystokinin action. Forty seven hamsters were divided into three groups: group I(n = 16) was fed on normal rodent chow(43% carbohydrate), group II(n = 14) was fed on a high CHO diet(65% carbohydrate), group III(n = 17) was fed on a high CHO diet containing 4% cholestyramine. Gallstones developed in 0% of group I, 42.9% of group II and 5.9% of group III(P< 0.05, group II vs III). To evaluate the chronic status of cholecystokinin level, the wet weight of pancreas and the average area of pancreatic acinar in microscopic high power field were measured. There was no significant difference between group II and group III in pancreatic weight and average area of pancreatic acinar(P> 0.05). In gallbladder bile analysis, there was also no significant difference between group II and group III in cholesterol, phospholipid, total calcium, total bilirubin and bile acid levels. In conclusion, cholestyramine decreases the frequency of pigment gallstone formation in high CHO diet-fed hamsters, but it is not clear whether the mechanism of cholestyramine decreasing the gallstone formation is due to the action of cholecystokinin.
Animal ; Bilirubin/metabolism ; Cholecystokinin/*analysis ; Cholelithiasis/*pathology ; Cholesterol/metabolism ; Cholestyramine/*administration & dosage ; Dietary Carbohydrates/*administration & dosage ; Female ; Gallbladder/*metabolism/pathology ; Hamsters ; Male ; Mesocricetus ; Organ Weight ; Pancreas/physiopathology ; Phospholipids/metabolism ; Pigmentation ; Support, Non-U.S. Gov't

OBJECTIVETo investigate the relationship between anatomic abnormalities and malfunction of Oddi sphincter with formation of bile duct pigment gallstone.

METHODSOne hundred and twenty-three patients with a T tube after cholecystectomy and choledochotomy were divided into reflux group and control group by measuring the amounts of radioactivity of (99m)Tc-DTPA in the bile. Among them 53 were selected randomly to undergo choledochoscopic manometry. Basal pressure of Oddi's sphincter (SOBP), amplitude of Oddi's sphincter (SOCA), frequency of contraction (SOF), duration of contraction (SOD), duodenal pressure (DP), common bile duct pressure (CBDP) were scored and analyzed. The level of plasma motilin and serum gastrin of 45 patients and 12 healthy volunteers were measured by radioimmunoassay. The incidence rates of duodenal descending part diverticulum in patients with bile duct pigment stones, patients without alimentary tract diseases, patients with gallbladder polyps, patients with gallbladder stones were studied by means of barium meal examination. The incidence rates of intraduodenal peri-ampullary diverticulum in patients with primary bile duct pigment stones, patients with bile duct stone and gallbladder stones, patients with bile duct stones originating from the gallbladder, patients with inflammation and stricture of the extremity of bile duct and papilla, patients with cancer of the extremity of bile duct and papilla, patients with post-cholecystectomy syndrome were detected by duodenoscope.

RESULTSOf the patients, 44 were detected with duodenal-biliary reflux (35.8%). SOBP, SOCA and CBDP in the reflux group were much lower than those in control group (P < 0.001). The level of serum gastrin and plasma motilin of the reflux group were much lower than those of control group (P < 0.01). Positive correlation was found between level of motilin and SOBP while level of gastrin was positively correlated with SOBP and CBDP. The incidence of duodenal diverticulum in patients with bile duct pigment stone was 36.62%, which was higher than that of the other 3 groups. The incidence rate of intraduodenal peri-ampullary diverticulum in patients with primary bile duct pigment stone was higher than that of patients with inflammation and stricture of the extremity of bile duct and papilla, patients with cancer of the extremity of bile duct and papilla and patients with bile duct stones originating from the gallbladder.

CONCLUSIONSThe patients with bile duct pigment stone have apparent duodenal-biliary reflux and infection of the bile duct. The state of structure and function of Oddi's sphincter is correlated significantly with bile duct pigment stone. The anatomic abnormalities and malfunction of Oddi's sphincter played an important role in the formation of bile duct pigment stone.

Adult ; Aged ; Aged, 80 and over ; Bile Pigments ; metabolism ; Cholelithiasis ; metabolism ; pathology ; physiopathology ; Female ; Gastrins ; blood ; Humans ; Male ; Middle Aged ; Motilin ; blood ; Pressure ; Radioimmunoassay ; Retrospective Studies ; Sphincter of Oddi ; pathology ; physiopathology