Can pigment gallstones be induced by biliary stricture and prevented by medicine in Guinea pigs?

AIM: To determine the relationship between biliary stricture and pigment gallstone formation, and the prevention of pigment gallstones with medicine. METHODS: One hundred and eighteen male guinea pigs were randomly divided into four groups: stricture group (S, n = 30) underwent partial ligation of common bile duct, and fed on regular chow; S plus medicine group (S+M, n = 27) underwent the same operation but fed on medicinal chow (0.3 g chenodeoxycholic acid, 0.5 g glucurolactone, and 0.5 g aspirin were mixed up in 1.2 kg regular chow); medicinal control group (C+M, n = 30) was free of operation, and fed on medicinal chow; and control group (C, n = 31) was free of operation and fed on regular chow. One week later, laparotomy was performed, and the bile of gallbladder was collected, measured, and cultured. RESULTS: Gallstones were identif ied. Pigment gallstones were induced by biliary stricture in 95% (22/23) of S group. In the S+M group, the incidence of gallstone was reduced to 55% (11/20, vs S group, P < 0.01). The changes of indirect bilirubin and ionized calcium in the bile were consistent with gallstone incidences. CONCLUSION: Biliary stricture can cause pigment gallstone formation in guinea pigs, and the medicines used can lower the incidence of gallstones. The bilirubin and ionized calcium play important roles in pigment gallstone formation.

Effects of Choleretics on Bile Compositions Drained from Patients with Pigment Gallstone

To provide evidence for three-level prevention of cholelithiasis by means of observing the effects of some choleretics on bile compositions drained from patients with pigment gallstone. Methods： Twenty-seven patients suffering from primary pigment gallstones and having received treatment of choledochostomies plus T-tube or endoscopic nasal bile drainage （ENBD） were divided equally into three groups, and administered respectively with Lidanling （利胆灵, the LDL group）, ursodesoxycholic acid （the UDA group） and combination of LDL and UDA （the LDL＋ UDA group） through oral intake（7 patients in each group）. Besides, 6 post-operational patients got no treatment with any drug were allocated in the control group. Bile of all the patients was collected before treatment and on the 1, 3, 5, 7th day after the treatment started to detect levels of total bile acid （TBA）, glycocholic acid （GCA）, taurocholic acid （TCA）, glycocholic cheno-desoxycholic acid （GCDCA）, total bilirubin （TBIL）, uncombined bilirubin （ UCB）, concentration of calcium ion （Ca^2＋ ） as well as the bacterio-genetic and endogenous 13-glucuronidase activity for comparing. Results： Levels of TBA, GCA, TCA and GCDCA got gradually increased in the UDA group and the LDL ＋ UDA group after treatment （ P〈0. 05）, while those in the LDL group remained unchanged, showing an insignificant difference as compared with those in the control group. In the LDL group and the LDL ＋ UDA group, TBIL gradually increased while UCB gradually decreased in the course of treatment （P〈0. 05）. Moreover, levels of Ca^2＋ and endogenous β-glucuronidase activity got significantly lowered （ P〈0. 05）. Conclusion： Combined use of LDL and UDA could elevate levels of TBA, GCA, TCA, GCDCA, enhance the excretion of TBIL in patients with pigment gallstone after bile drainage, lower levels of UCB and Ca^2＋ and the activity of endogenous β-glucuronidase in the bile, so as to reduce the possibility of stone formation of bile, and therefore, it could be used to prevent the production of pigment gallstone, especially to prevent post-operative recurrence of stones.

Gallstones in patients with liver cirrhosis:Incidence,etiology,clinical and therapeutical aspects

Gallstones occur in about one third of the patients having liver cirrhosis.Pigment gallstones are the most frequent type,while cholesterol stones represent about15%of all stones in cirrhotics.Increased secretion of unconjugated bilirubin,increased hydrolysis of conjugated bilirubin in the bile,reduced secretion of bile acids and phospholipds in bile favor pigment lithogenesis in cirrhotics.Gallbladder hypomotility also contributes to lithogenesis.The most recent data regarding risk factors for gallstones are presented.Gallstone prevalence increases with age,with a ratio male/female higher than in the general population.Chronic alcoholism,viral C cirrhosis,and non-alcoholic fatty liver disease are the underlying liver diseases most often associated with gallstones.Gallstones are often asymptomatic,and discovered incidentally.If asymptomatic,expectant management is recommended,as for asymptomatic gallstones in the general population.However,a closer follow-up of these patients is necessary in order to earlier treat symptoms or complications.For symptomatic stones,laparoscopic cholecystectomy has become the therapy of choice.Child-Pugh class and MELD score are the best predictors of outcome after cholecystectomy.Patients with severe liver disease are at highest surgical risk,therefore gallstone complications should be treated using noninvasive or minimally invasive procedures,until stabilization of the patient condition.

Roles of sphincter of Oddi motility and serum vasoactive intestinal peptide,gastrin and cholecystokinin octapeptide

AIM: To investigate roles of sphincter of Oddi (SO) motility played in pigment gallbladder stone formation in model of guinea pigs.

Role of osteopontin in diet-induced brown gallstone formation in rats

Background:Although osteopontin(OPN)is expressed in the liver and pigment gallstones of patients with hepatolithiasis,its role in pigment gallstone formation remains unclear.This study aimed to explore the function of OPN in pigment gallstone formation.Methods:Rats were fed a chow diet(CD)or lithogenic diet(LD)for 10 consecutive weeks;blocking tests were then performed using an OPN antibody(OPN-Ab).Incidence of gallstones and levels of several bile components,OPN,tumor necrosis factor alpha(TNF-α),and cholesterol 7 alpha-hydroxylase(CYP7A1)were analyzed.To determine TNF-αexpression in hepatic macrophages and both CYP7A1 and bile acid(BA)expression in liver cells,recombinant rat OPN and recombinant rat TNF-αwere used to treat rat hepatic macrophages and rat liver cells,respectively.Chi-square or Fisher exact tests were used to analyze qualitative data,Student t-test or one-way analysis of variance were used to analyze qualitative data.Results:Incidence of gallstones was higher in LD-fed rats than in CD-fed rats(80%vs.10%,P<0.05).BA content significantly decreased in bile(t=-36.08,P<0.01)and liver tissue(t=-16.16,P<0.01)of LD-fed rats.Both hepatic OPN protein expression(t=9.78,P<0.01)and TNF-αlevel(t=8.83,P<0.01)distinctly increased in the LD group;what’s more,CYP7A1 mRNA and protein levels(t=-12.35,P<0.01)were markedly down-regulated in the LD group.Following OPN-Ab pretreatment,gallstone formation decreased(85%vs.25%,χ^(2)=14.55,P<0.01),liver TNF-αexpression(F=20.36,P<0.01)was down-regulated in the LD group,and CYP7A1 expression(F=17.51,P<0.01)was up-regulated.Through CD44 and integrin receptors,OPN promoted TNF-αproduction in macrophage(F=1041,P<0.01),which suppressed CYP7A1 expression(F=48.08,P<0.01)and reduced liver BA synthesis(F=119.4,P<0.01).Conclusions:We provide novel evidence of OPN involvement in pigmented gallstone pathogenesis in rats.