Hormonal regulation of bicarbonate secretion in the biliary epithelium.

Bicarbonate excretion in bile is a major function of the biliary epithelium. It is driven by the apically located Cl-/HCO3- exchanger which is functionally coupled with a cAMP-dependent Cl- channel (CFTR). A number of hormones and/or neuropeptides with different mechanisms and at different intracellular levels regulate, in concert, the processes underlying bicarbonate excretion in the biliary epithelium. Secretin induces a bicarbonate rich choleresis by stimulating the activity of the Cl-/HCO3- exchanger by cAMP and protein kinase A mediated phosphorylation of CFTR regulatory domain. Protein phosphatase 1/2A are involved in the run-down of secretory stimulus after secretin removal. Acetylcholine potentiates secretin-choleresis by inducing a Ca(++)-calcineurin mediated "sensitization" of adenyl cyclase to secretin. Bombesin and vasoactive intestinal peptide also enhance the Cl-/HCO3- exchanger activity, but the intracellular signal transduction pathway has not yet been defined. Somatostatin and gastrin inhibit basal and/or secretin-stimulated bicarbonate excretion by down-regulating the secretin receptor and decreasing cAMP intracellular levels induced by secretin

Variations in pigment and carbohydrate content of gallbladder bile affect accurate quantitation of total protein when using the fluorescamine method

Background: Despite solute dilution and reduced total lipid concentrations, an unexplained increase in protein concentration has been reported to occur in the gallbladder bile of cholesterol gallstone patients. Methods: Solutes in gallbladder bile from gallstone-free controls and from four study groups were measured using standard methods. Total proteins were measured using amino acid analysis and a conventional fluorescamine method. Results: Bile salts and pigment content were greater in gallstone-free controls than in all other study groups, including morbidly obese gallstone-free subjects. Total biliary protein concentration, as determined by amino acid analysis in the gallstone-free control group was higher than in non-obese gallstone patients with multiple stones and in morbidly obese gallstone-free subjects. Total biliary proteins as measured with fluorescamine, however, did not show intergroup differences. A major problem of the conventional fluorescamine assay is shown to be an artefact arising from the high pigment content of the more concentrated samples. Conclusions: Very dilute gallbladder bile samples are often found in the presence of gallstone disease. This also occurs in morbidly obese subjects, even in the absence of gallstones. Although the contribution of protein secretion/absorption by the gallbladder can also be relevant, especially in the presence of morbid obesity, the protein concentration in gallbladder bile, when accurately measured, generally parallels the concentrations of non-absorbed biliary solutes, reflecting the efficiency of fluid absorption. Measurement of biliary proteins by the conventional fluorescamine method is unreliable in clinical studies in which intergroup differences in pigment content are commonly present

Human gallbladder mucosal function : effects on intraluminal fluid and lipid composition in health and disease.

Abstract: Gallbladder mucosal absorption of fluid during fasting is a well-known process. Indirect in vivo and recent in vitro evidence for physiologically relevant gallbladder absorption of cholesterol and phospholipids from bile has been observed in humans. The present study explored and compared by indirect means the relative efficiences of human gallbladder mucosal absorption of fluid and lipids in health and disease. Biliary lipids and pigment content were measured in fasting gallbladder bile samples obtained from gallstone-free controls and from four study groups: multiple and solitary cholesterol gallstone patients, and morbidly obese subjects with and without gallstones. Bile salts and pigment content were significantly greater in gallstone-free controls than in all other disease study groups, This was interpreted as evidence of more effective gallbladder mucosal fluid absorption in nonobese gallstone-free controls compared to that in all other groups, Correlation plot analyses of biliary lipids showed lower concentrations of phospholipids than expected from the index bile salt concentrations, The same was found for cholesterol concentrations but only in supersaturated samples, These findings were much more pronounced in gallstone free-controls and were accordingly interpreted as evidence of more efficient gallbladder absorption of both phospholipids and cholesterol in controls compared with that found in each of the disease study groups, Moreover, impaired gallbladder mucosal function, while invariably associated with cholesterol gallstone disease, was not found to be a necessary consequence of the physical presence of stones. It is concluded that efficient gallbladder mucosal absorption of both fluid and apolar lipids from bile is a normal physiological process that is often seriously impaired in the presence of either cholesterol gallstone disease or at least one of its precursor forms

Nonabsorbable disaccharides plus neomycin in hepatic encephalopathy: do they enhance each other?

[No abstract available

Rapid determination of plasma ammonia using an ion specific electrode

A method for measuring directly the ammonia concentration in plasma by the use of an ammonia gas sensitive electrode is proposed. The plasma pH is brought to a final value of 10.4; at which pH, no NH3 is released from other sources and the amount of NH3 measured is 92% of the total ammonia (pKa = 9.3). The potentiometric readings of the samples are referred to a standard curve. In normal subjects, the mean values of venous ammonia nitrogen are 23.9 ± 9.6 (SD) μg/100 ml of plasma. Reproducibility is ± 0.5 mV, or 2%. The method was also compared to the ion exchange method: The difference was constantly below 3%. The time required for the assay is less than 10 min. The method, when compared to others adopting the same electrode, is recommended for its simplicity, accuracy, and rapidity. © 1975

NONSURGICAL APPROACH TO GALLSTONES - ORAL-THERAPY WITH BILE-ACIDS

Gallstone disease is very common. According to recent epidemiological studies it affects 6.4% of men and 10.4% of women between 30-69 years of age. In more than half of these the disease remains asymptomatic. Until fairly recently cholecystectomy was the only available treatment. However, in the early '70's, ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) were introduced as possible alternatives to surgery. Nonetheless, not everyone with gallstones can or should be given this type of treatment. Whilst it is commonly agreed that symptomatic gallstones must be operated on, there is no such agreement regarding treatment with biliary acid per os for asymptomatic stones. However, only asymptomatic subjects with radiolucent stones in a functioning gallbladder, no larger than 15 mm in diameter, can be treated with a good rate of success-as high as 50% after one year of treatment. The biliary acid currently used, either alone or together with CDCA, is UDCA. The average dose is 8-10 mg/kg/day. There are few side effects and in practice there are no contraindications to such treatment. The cost of the treatment is not prohibitive: 750 mg/day of UDCA in Italy costs about $1540 for a year's supply