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PubMed1990

Free fatty acids stimulate mucin hypersecretion by rabbit gall-bladder epithelium in vitro.

1. Mucin, a high-molecular-weight glycoprotein secreted by the gall-bladder and biliary duct epithelium, is a well-known nucleation-prompting factor in experimental and human gall-stone disease. 2. Free fatty acids when incubated in vitro (micellar suspension with 1 mmol/l Tween 40) with rabbit gall-bladders can promote abundant mucus secretion. 3. The hexosamine content of rabbit gall-bladder walls, measured by gas-liquid chromatography, was significantly higher in gall-bladders incubated with fatty acids than in control tissues. 4. The biochemical data were supported by ultrastructural findings showing numerous droplets with a translucent content in the perinuclear cytoplasm. Exocytosis was also seen in treated gall-bladders, confirming the secretory nature of the vesicles. 5. These results suggest that free fatty acids, which appear in high amounts when bile lecithins are hydrolysed by phospholipase, play an active role in the gall-stone formation.

Acetylgalactosamine↗
PubMed1999

The effect of curcumin and placebo on human gall-bladder function: an ultrasound study.

BACKGROUND: The extract of medicinal plants containing curcumin is traditionally believed to have a positive contraction effect on the human gall-bladder. AIMS: To compare the effect of 20 mg curcumin or placebo on the gall-bladder volume of healthy volunteers. METHODS: A randomized, double blind and crossover design study was carried out in 12 healthy volunteers (seven males and five females). Ultrasonography examination was carried out serially to measure the gall-bladder volume. The data obtained was analysed by paired Student's t-test. RESULTS: The fasting gall-bladder volumes of 15.74 +/- 4.29 mL on curcumin and 15.98 +/- 4.08 mL on placebo were similar (P > 0.20). The gall-bladder volume was reduced within the period after curcumin administration. The percentage of gall-bladder volume reduction at 0.5, 1.0, 1.5 and 2.0 h after 20 mg curcumin administration were 11.8 +/- 6.9, 16.8 +/- 7.4, 22.0 +/- 8.5 and 29. 3 +/- 8.3%, respectively, which was statistically significant compared to placebo. CONCLUSION: On the basis of the present findings, it appears that curcumin induces contraction of the human gall-bladder.

Adult↗
PubMed2000

Review article: gall-bladder motor function in obesity.

A number of epidemiological studies has established obesity as a risk factor for gallstone disease. More recently, studies have suggested a relationship between gallstone disease and the metabolic syndrome linked to central adiposity, whose cardinal feature is represented by hyperinsulinaemia. Studies on fasting gall-bladder volume in obese subjects show that this parameter correlates with weight, body mass index (BMI) and body surface area; however, this is also true for large-sized non-obese subjects. Gall-bladder volume also correlates with abdominal fat and with impaired glucose tolerance. In contrast to the well-established role of bile supersaturation in the pathogenesis of gallstones in obesity, data are controversial on whether gall-bladder motor function is defective in obese subjects. However, studies were heterogeneous for subjects' BMI, emptying stimulus, technique used and parameters assessed to evaluate gall-bladder motor function. Also, differences in baseline gall-bladder volume may lead to wide differences in bile 'washout' effect despite apparently similar percentage changes in volume or content. Although post-prandial plasma levels of cholecystokinin (CCK) are normal in obese subjects, there is some evidence that a sub-group of obese subjects could have decreased sensitivity to CCK, possibly mediated by hyperinsulinaemia. Further studies using standard physiological stimuli and controlling for glucose tolerance, fasting insulin levels and baseline gall-bladder volume are needed to establish the role of gall-bladder motor function in the pathogenesis of gallstone disease in obesity.

Body Mass Index↗
PubMed2004

Lipase inhibition by orlistat: effects on gall-bladder kinetics and cholecystokinin release in obesity.

BACKGROUND: Obese subjects are at risk of developing gallstones as a result of the obese state and during weight reduction. AIM: To study whether orlistat, by lipase inhibition, impairs gall-bladder emptying, thus further predisposing weight-losing obese subjects to gallstone formation. METHODS: Patients entering a randomized clinical trial of 1 month of diet, followed by treatment with placebo, 3 x 60 mg orlistat or 3 x 120 mg orlistat, underwent gall-bladder emptying studies measured by ultrasound. Meal-induced cholecystokinin release and gall-bladder emptying were investigated at the start, at randomization and after 1 and 12 months. RESULTS: One month of dieting did not change gall-bladder emptying and cholecystokinin release. After 1 month, placebo treatment resulted in a decreased fasting volume of 11%, compared with increases of 26% and 47% with 60 and 120 mg orlistat, respectively. Gall-bladder emptying increased by 9% with placebo and decreased by 15% and 53% with 60 and 120 mg orlistat, respectively. Fasting cholecystokinin values and cholecystokinin release decreased significantly in the orlistat group. After 1 year, a persistent but attenuated effect of orlistat on gall-bladder emptying and cholecystokinin release remained. Three of 40 patients developed gallstones, two on placebo with major weight loss and one on 60 mg orlistat. CONCLUSIONS: One month of lipase inhibition by orlistat significantly impaired gall-bladder motility, which persisted to some extent after 1 year. Obese subjects with diabetes or hyperlipidaemia, who are more at risk of gallstones, should be followed carefully.

Adult↗
PubMed2003

Characterization of the intrinsic and extrinsic innervation of the gall bladder epithelium in the Australian Brush-tailed possum (Trichosurus vulpecula).

Intrinsic neurones of the gall bladder modulate its function. Nitric oxide synthase (NOS) and vasoactive intestinal polypeptide (VIP) are present in gall bladder neurones and nitric oxide and VIP modulate its epithelial functions. As an extensive extrinsic innervation of the gall bladder is also present, the source of the epithelial innervation is unclear. In this study the source of the gall bladder epithelial innervation is defined. Immunoreactivity for VIP, NOS, substance P (SP), calcitonin gene related peptide (CGRP) and tyrosine hydroxylase (TH) in organotypic cultured and freshly fixed gall bladder were compared. Retrograde tracing in vitro from the epithelium was used to identify putative intrinsic secretomotor neurones, which were then characterized by immunohistochemistry. Abundant spinal afferent and sympathetic innervation of the gall bladder epithelium was demonstrated by CGRP/SP and TH immunohistochemistry, respectively. The intrinsic secretomotor innervation of the epithelium is derived exclusively from neurones of the subepithelial plexus. A majority of these neurones were immunoreactive for NOS. Some of the NOS-immunoreactive neurones of the subepithelial plexus also contained VIP and/or SP. Gall bladder subepithelial plexus neurones, containing NOS and/or VIP/SP, innervate the epithelium, as do extrinsic neurones.

Animals↗
PubMed2002

Effect of different curcumin dosages on human gall bladder.

Our previous study demonstrated that curcumin, an active compound of Curcuma xanthorrhiza and C. domestica, produces a positive cholekinetic effect. A 20 mg amount of curcumin is capable of contracting the gall bladder by up to 29% within an observation time of 2 h. The aim of the current study was to define the dosage of curcumin capable of producing a 50% contraction of the gall bladder, and to determine if there is a linear relationship between doubling the curcumin dosage and the doubling of gall bladder contraction. A randomised, single-blind, three-phase, crossover-designed examination was carried out on 12 healthy volunteers. Ultrasonography was carried out serially to measure the gall bladder volume. The data obtained was analysed by analysis of variance (ANOVA). The fasting volumes of gall bladders were similar (P > 0.50), with 17.28 +/- 5.47 mL for 20 mg curcumin, 18.34 +/- 3.75 mL for 40 mg and 18.24 +/- 3.72 mL for 80 mg. The percentage decrease in gall bladder volume 2 h after administration of 20, 40 and 80 mg was 34.10 +/- 10.16, 51.15 +/- 8.08 and 72.25 +/- 8.22, respectively, which was significantly different (P < 0.01). On the basis of the present findings, it appears that the dosage of cucumin capable of producing a 50% contraction of the bladder was 40 mg. This study did not show any linear relationship between doubling curcumin dosage and the doubling of gall bladder contraction.

Administration, Oral↗
PubMed1998

The never ripe mutant provides evidence that tumor-induced ethylene controls the morphogenesis of agrobacterium tumefaciens-induced crown galls on tomato stems

We confirm the hypothesis that Agrobacterium tumefaciens-induced galls produce ethylene that controls vessel differentiation in the host stem of tomato (Lycopersicon esculentum Mill.). Using an ethylene-insensitive mutant, Never ripe (Nr), and its isogenic wild-type parent we show that infection by A. tumefaciens results in high rates of ethylene evolution from the developing crown galls. Ethylene evolution from isolated internodes carrying galls was up to 50-fold greater than from isolated internodes of control plants when measured 21 and 28 d after infection. Tumor-induced ethylene substantially decreased vessel diameter in the host tissues beside the tumor in wild-type stems but had a very limited effect in the Nr stems. Ethylene promoted the typical unorganized callus shape of the gall, which maximized the tumor surface in wild-type stems, whereas the galls on the Nr stems had a smooth surface. The combination of decreased vessel diameter in the host and increased tumor surface ensured water-supply priority to the growing gall over the host shoot. These results indicate that in addition to the well-defined roles of auxin and cytokinin, there is a critical role for ethylene in determining crown-gall morphogenesis.

Journal Article↗
PubMed1993

In vivo regulation of mucosal transport of H+ and HCO3- in the feline gall bladder.

In the gall bladder of a fasting subject, a decline in the pH of the contents occurs due to secretion of H+ from the mucosa. In this study in anaesthetized cats, the gall bladder lumen was perfused with a bicarbonate buffer bubbled with 4% CO2 in air. During basal conditions, the PCO2 always rose while the pH and [HCO3-] fell in the buffer when passing through the gall bladder lumen, indicating a continuous secretion of H+ by the mucosa. This H+ secretion was enhanced by stimulation of the respective sympathetic nerves and was blocked by intraluminal amiloride. Intravenous infusion of vasoactive intestinal peptide (VIP) raised the pH and [HCO3-] in the buffer during the passage through the gall bladder lumen, indicating a secretion of bicarbonate from the mucosa. In view of the presence of sympathetic and VIP immunoreactive nerve fibres in the gall bladder wall and VIP receptors on the luminal epithelial cells, the study demonstrates that there are functional grounds for physiological variations in the secretion of H+ and HCO3- by the gall bladder mucosa. These variations may be important for the solubility of calcium salts in the gall bladder contents.

Amiloride↗
PubMed1987

Pressure changes in canine gall-bladder associated with emptying.

1. For decades it has been supposed that emptying of the gall-bladder follows a rise in gall-bladder pressure of some 10-15 mmHg and relaxation of the sphincter of Oddi. 2. This subject has been re-examined in dogs chronically fitted with fistulas, using a model which does not entail interference with either the bile duct or sphincter of Oddi. 3. The pressure in the gall-bladder was recorded continuously under fasting conditions, after feeding and after intravenous infusion of the octapeptide of cholecystokinin (CCK-OP) in six dogs. 4. Gall-bladder pressure showed a modest sustained rise of 2-3 mmHg following ingestion of food and intravenous infusions of CCK-OP (125 ng kg-1 h-1). 5. During half of the experiments a transient rise of 3-10 mmHg lasting 2-3 min was observed after feeding and following infusion of I.V. CCK-OP (125 ng kg-1 h-1). Emptying of the gall-bladder, measured by bilirubin output from the biliary fistula, started shortly before the peak rise in pressure occurred. 6. We conclude that a significant rise in gall-bladder pressure is not a prerequisite for emptying and that the pressure changes occurring physiologically are smaller than have been reported previously. 7. We believe that the larger pressure changes recorded in the past may have been produced because of resistance to bile flow introduced by the models employed. 8. Emptying of the gall-bladder, in the dog, appears to have occurred within 40 min of the ingestion of food, suggesting that the cephalic and gastric phases of this process are quantitatively more important than has been thought previously.

Animals↗
PubMed2006

Agrobacterium rhizogenes GALLS protein contains domains for ATP binding, nuclear localization, and type IV secretion.

Agrobacterium tumefaciens and Agrobacterium rhizogenes are closely related plant pathogens that cause different diseases, crown gall and hairy root. Both diseases result from transfer, integration, and expression of plasmid-encoded bacterial genes located on the transferred DNA (T-DNA) in the plant genome. Bacterial virulence (Vir) proteins necessary for infection are also translocated into plant cells. Transfer of single-stranded DNA (ssDNA) and Vir proteins requires a type IV secretion system, a protein complex spanning the bacterial envelope. A. tumefaciens translocates the ssDNA-binding protein VirE2 into plant cells, where it binds single-stranded T-DNA and helps target it to the nucleus. Although some strains of A. rhizogenes lack VirE2, they are pathogenic and transfer T-DNA efficiently. Instead, these bacteria express the GALLS protein, which is essential for their virulence. The GALLS protein can complement an A. tumefaciens virE2 mutant for tumor formation, indicating that GALLS can substitute for VirE2. Unlike VirE2, GALLS contains ATP-binding and helicase motifs similar to those in TraA, a strand transferase involved in conjugation. Both GALLS and VirE2 contain nuclear localization sequences and a C-terminal type IV secretion signal. Here we show that mutations in any of these domains abolished the ability of GALLS to substitute for VirE2.

Adenosine Triphosphate↗
PubMed1985

Effect of vegetarianism on development of gall stones in women.

Real time ultrasonography was used to compare the prevalence of gall stones in two groups of women aged 40-69: 632 women recruited from general practice registers and 130 vegetarians. One hundred and fifty-six (25%) of the 632 women who ate meat and 15 (12%) of the 130 vegetarian women either had gall stones visible on ultrasonography or had previously undergone cholecystectomy (p less than 0.01). The prevalence of gall stones was found to increase with age and body mass index. The 2.5 fold increase in risk of developing gall stones in non-vegetarians compared with vegetarians was reduced to 1.9 when controlling for these two potentially confounding factors, but remained significant. A family history of gall stones was reported more often by women with gall stones, but no association was found with parity or use of exogenous oestrogens. Thus the importance of age and obesity to determine the prevalence of gall stone was confirmed, and a dietary factor associated with vegetarianism may prevent this common condition.

Adult↗
PubMed1989

Quantitative measurement of biliary excretion and of gall bladder concentration of drugs under physiological conditions in man.

Gall bladder storage of hepatic bile prevents complete recovery of biliary excretion of drugs to be obtained under physiological conditions in man. The aim of this study was to develop and validate a method for simultaneous measurement of gall bladder storage of a cholephilic drug, and of its duodenal excretion and t1/2 in bile. Duodenal perfusion using polyethylene glycol as intestinal recovery marker for measurement of drug duodenal excretion, with an iv bolus of 99mTc HIDA for measurement of drug mass within the gall bladder was used. Gall bladder volume was measured by ultrasonography. T1/2 in bile was measured by relating drug duodenal excretion to that of bile acid used as an endogenous bile marker. The use of bile acid as biliary marker was validated in two subjects receiving simultaneous iv infusion of indocyanine green. Seven healthy subjects were studied using a beta-lattam antibiotic, Cefotetan 1 g iv, as test drug. Median values during the study period (seven hours) were 51.1 mg for Cefotetan duodenal excretion, 45.2 mg for gall bladder mass and 2.8 mg/ml for concentration within the gall bladder. T1/2 of the drug in bile was 100 minutes. This technique enables measurement of mass and concentration of drugs within the gall bladder to be carried out, in addition to measurements of t1/2 of drugs in bile. These measurements may have specific application for assessment of potential efficacy of antibiotics in biliary tract infections, as well as general application for assessment of biliary excretory kinetics of drugs.

Adult↗
PubMed1990

Plasma insulin, serum lipids and lipoproteins in gall stone disease in non-insulin dependent diabetic subjects: a case control study.

Fasting insulin, lipids and lipoproteins were measured in 22 middle aged female non-insulin dependent diabetics with gall stone disease (cases) and in 22 non-insulin dependent diabetics without gall stone disease (controls). The groups were matched for sex, age, obesity, and fasting glucose concentrations. No differences were observed between the cases and controls in duration of diabetes, glycated haemoglobin A1, alcohol intake, smoking, use of cardiovascular drugs or a history of myocardial infarction. Diabetics with gall stone disease had higher fasting insulin concentrations (p less than 0.5), lower total (p less than 0.01) and low density lipoprotein cholesterol (p less than 0.01) and high density lipoprotein cholesterol (not statistically significant) concentrations than diabetics without gall stone disease. These changes in insulin, lipids and lipoproteins are similar to reported changes in non-diabetic subjects with gall stone disease. Therefore, they are characteristic for gall stone disease and not as such explanatory to an increased risk of gall stones in patients with non-insulin dependent diabetes.

Case-Control Studies↗
PubMed1991

Symptomatic and silent gall stones in the community.

The prevalence of gall stone disease in a stratified random sample of 1896 British adults (72.2% of those approached) was established using real time ultrasound. The prevalence rose with age, except in women of 40-49 years, so that at 60-69 years, 22.4% of women and 11.5% of men had gall stones or had undergone cholecystectomy. The cholecystectomy rate of people with gall stone disease was higher in women than in men (43.5% v 24%, p less than 0.05). Very few subjects with gall stones had convincing biliary symptoms. In women, 10.4% had symptoms according to a questionnaire definition of biliary pain and 6.3% according to conventional history taking, while no men at all admitted to biliary pain. Nevertheless, cholecystectomy in men had nearly always been preceded by convincing biliary symptoms. The age at cholecystectomy was, on average, nine years less than the age at detection of silent gall stones in both sexes. It is concluded that either gall stones are especially prone to cause symptoms in younger people or that there are two kinds of cholelithiasis - symptomatic and silent. The lack of symptomatic gall stones in cross sectional surveys is probably due to their rapid diagnosis and treatment.

Adult↗
PubMed1993

Primary culture of bovine gall bladder epithelial cells.

Gall bladder epithelial cells serve numerous biological functions and abnormalities in their function are important in the pathogenesis of several gall bladder diseases. Direct studies on cell function are rare due to lack of reliable methods to culture this epithelium. This study reports a reliable and reproducible method of harvesting and culturing gall bladder epithelial cells. Normal bovine gall bladder epithelium, obtained within 20 minutes of slaughter, was rinsed with modified Hanks's balanced salt solution, the mucosa separated and incubated in trypsin--EDTA solution at 37 degrees C. The cells were isolated and resuspended in Dulbeco's modification of Eagles' medium containing 10% fetal calf serum and, after filtration and centrifugation, were plated under aseptic conditions. The growth rate was established by flow cytometry and the morphological characteristics of the growing cells by electron microscopy. Gall bladder epithelial cells grew successfully and visible clusters of cells were present by day two, confluency being reached at 8 to 10 days in collagen coated plates and 12 to 14 days in uncoated plates. Electron microscopy showed typical gall bladder epithelia with microvilli, tight junctions, and mucus droplets. This method proved reliable and reproducible for the culture of gall bladder epithelial cells and should allow direct studies of the biological properties of these cells in human tissue.

Animals↗
PubMed1993

Non-communicating multiseptate gall bladder and choledochal cyst: a case report and review of publications.

A 14 year old girl with multiseptate gall bladder and cystic dilatation of the biliary tree is presented. This is the 20th published case report of patients with multiseptate gall bladder and only the second to be associated with a choledochal cyst. The cystic spaces of the gall bladder did not communicate with the neck of the gall bladder or the rest of the biliary tree, and this unusual feature has not been previously described. A multiseptate gall bladder with a normal biliary tree commonly causes symptoms suggestive of cholecystitis, although gall stones are seldom present. Diagnosis is confirmed by an oral cholecystogram or ultrasound scan that may show the fine intraluminal septae, and these features should be looked for in patients with biliary symptoms without biliary calculi. Cholecystectomy is curative for the isolated gall bladder anomaly but hepaticojejunostomy may be necessary for an associated choledochal cyst.

Adolescent↗
PubMed1995

Effects of simvastatin and cholestyramine on bile lipid composition and gall bladder motility in patients with hypercholesterolaemia.

Although the effects of 3-hydroxy, 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and bile acid sequestrants on bile lipid composition have been studied separately, no data are available on combination therapy of these drugs. Moreover, the effects of prolonged (four weeks) administration of these drugs on gall bladder motility, an important determinant of cholesterol gall stone formation, have not been studied so far. A prospective study was therefore performed with eight patients who had hypercholesterolaemia (age 53 (5) (SEM), body mass index 27.4 (1.1) kg m-2, low density lipoprotein cholesterol 5.9 (0.3) mmol/l). They received treatment during three periods of four weeks with simvastatin 20 mg/day, cholestyramine 4 g twice daily, and a combination of both in random order, each treatment period separated by a two week wash out period. Before treatment and after each treatment period, postprandial gall bladder motility was studied with ultrasound, followed by duodenal bile sampling. Serum cholesterol decreased in all subjects in any treatment period illustrating good compliance. Molar percentages in duodenal bile of cholesterol, phospholipids, and bile salts were unchanged during simvastatin and cholestyramine treatment. During combined therapy percentage bile salts was lower (72.5 (2.9)% v 77.8 (1.7)% at baseline, p < 0.05) whereas phospholipids were higher (21.2 (2.4)% v 16.4 (1.3)% at baseline, p < 0.05). As a result cholesterol saturation index (CSI) did not change in any treatment period. No cholesterol crystals were detected in any bile sample, taken at baseline and after each treatment period. Bile salt hydrophobicity index during cholestyramine (0.19 (0.02)) and combined treatment (0.22 (0.01)) decreased strongly compared with baseline (0.34 (0.01), p < 0.001, p < 0.01, respectively), resulting from increased proportions of glycocholate (59.4 (3.9)% (cholestyramine), 55.6 (2.4)% (combination), and 28.2 (2.2) (baseline), p < 0.001)) and decreased proportions of deoxycholic acid and chenodeoxycholic acid. Fasting gall bladder volume was increased during simvastatin (28.7 (2.8) ml) v baseline (23.2 (2.3) ml, p < 0.01) whereas, residual volume did not differ (5.7 (0.9) ml (simvastatin) v 5.9 (0.7) (baseline). During cholestyramine and combined treatment, no significant differences in gall bladder motility were seen. In conclusion, this study suggests that HMG-CoA reductase inhibitors alone and combined with cholestyramine do not affect major determinants of cholesterol gall stone formation, for example, CSI and gall bladder emptying. In addition cholestyramine alone and combined with simvastatin leads to a strong decrease of bile salt hydrophobicity, which may be beneficial in the prevention of nucleation of cholesterol crystals.

Anticholesteremic Agents↗
PubMed1997

Increased incidence of biliary sludge and normal gall bladder contractility in patients with high spinal cord injury.

BACKGROUND: Patients with spinal cord injury (SCI) have an increased prevalence of gallstones. AIMS: To study prospectively the incidence of gallstones and gall bladder contractility in patients with SCI. PATIENTS AND METHODS: Thirty six consecutive patients with SCI were studied: 18 patients with SCI above thoracic 10 neuronal segment (> T10) and 18 patients with SCI below T10 (< T10). An equal number each of disease controls (multiple fractures) and healthy controls were also studied. All patients and controls underwent serial ultrasonography to detect development of gallstones and ultrasonographic measurement of gall bladder contractility. RESULTS: A significantly higher number (9/18) of patients with SCI > T10 developed biliary sludge compared with patients with SCI < T10 (2/18), disease controls (2/18), and healthy controls (1/18) (p < 0.05). No patient developed gallstones. The gall bladder fasting volume was significantly decreased in patients with SCI > T10 (20.56 ml; 95% confidence intervals (CI) 19.74 to 21.38) compared with that in patients with SCI < T10 (27.33 ml, 95% CI 26.17 to 28.49; p < 0.05), disease controls (27.92 ml, 95% CI 26.69 to 29.15; p < 0.05), and healthy controls (28.35 ml, 95% CI 27.25 to 29.45; p < 0.05). Gall bladder contractility was normal in patients with SCI as shown by normal gall bladder residual volume and emptying time. CONCLUSIONS: Patients with SCI above T10 have an increased incidence of biliary sludge and a decreased gall bladder fasting volume. Gall bladder contractility is, however, normal.

Adult↗