Mechanisms of Dissolution of Human Cholesterol Gallstones

Higuchi, William I.; Prakongpan, Sompol; Young, Fudah

doi:10.1002/jps.2600620618

Cited by 44 publications

(30 citation statements)

References 10 publications

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“…This convective flow will always arise from the density differences caused by the cholesterol concentration gradient from the stone surface to the bulk solution. Under these conditions, dissolution is slower than suggested by many earlier measurements (24). In sodium taurocholate/lecithin/cholesterol at 10:30:0, this slower value is 7 X 10-8 gcm 2sec-1 for a 0.1-cm-diameter stone and 3.5 X 10-8 g* cm-2-sec-1 for a 1.0-cm stone (21).…”

Section: Methodsmentioning

confidence: 48%

Cholesterol monohydrate growth in model bile solutions.

Toor¹,

Evans²,

Cussler³

1978

Proc. Natl. Acad. Sci. U.S.A.

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The growth of cholesterol monohydrate from solutions of bile salt,lecithin, and small electrolytes has been studied by microscopy and with the Coulter Counter. The crystal forms found by micocopy are the same as those seen in human gallstones and in squirrel monkey cholesterol microliths. The cholesterol growth rates determined with the Coulter Counter vary slowly with cholesterol concentration at low degree of supersaturation but become exponential at higher cholesterol concentrations. Growth is accelerated by the presence of calcium and magnesium but inhibited by potassium. These results can be combined with previous measurements of cholesterol dissolution rates to give a more accurate picture of the dynamics of gallstone formation. The complex nature of real bile, in which many factors may change from sample to sample, makes it difficult to study nucleation and growth systematically.

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Section: Methodsmentioning

confidence: 48%

Cholesterol monohydrate growth in model bile solutions.

Toor¹,

Evans²,

Cussler³

1978

Proc. Natl. Acad. Sci. U.S.A.

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“…4. The decrease of dissolution rate on the 'addition of lecithin, which has also been observed bv others (13)(14)(15), is counter to that expected from the increased solubility of cholesterol caused by the addition of lecithin. No single step controls dissolution in this region.…”

Section: And Discussioncontrasting

confidence: 41%

“…Thus the results are most conveniently described in terms of three regions: stagnant bile, slow bile flow, and fast bile flow. Previous studies have been hampered because these regions have not been adequately defined (13)(14)(15). As a result, the different mechanisms involved have not been delineated.…”

Section: And Discussionmentioning

confidence: 99%

Accelerating Gallstone Dissolution

Tao

Cussler

Evans

1974

Proc. Natl. Acad. Sci. U.S.A.

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The dissolution rates of cholesterol in model bile salt solutions are controlled by diffusion in slowly flowing bile and by interfacial kinetics in rapidly flowing bile. At low flow, dissolution varies with the square root of bile flow and can be predicted, apriori, from existing correlations of mass transfer. At high bile flow, dissolution is independent of bile flow and is probably dominated by the rate of micelle adsorption. These results show that cholesterol gallstone dissolution, a potential nonsurgical therapy for cholelithiasis, can be accelerated little in slow bile, but more significantly in rapidly flowing bile.

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“…This would suggest that the same combination of properties, i.e., hydrophobic interaction and counterion binding, which optimize the rate of formation of bile saltlecithin micelles is also required for enhancing the equilibrium solubility of cholesterol in this mixed micellar system. CONCLUSIONS AND PHYSIOLOGICAL IMPLICATIONS Investigation of the dissolution of both cholesterol monohydrate and human gallstones by both bile salts and bile salt lecithin mixed media by Higuchi and coworkers (17,18) has shown that the dissolution is interfacially controlled. It was observed in these studies that the addition of lecithin to the dissolution media containing the bile salt reduced the dissolution rates even though it increased the equilibrium solubility of cholesterol monohydrate in the dissolution media (19).…”

Section: Resultsmentioning

confidence: 98%

Kinetics and Thermodynamics of Dissolution of Lecithin by Bile Salts

Lindenbaum

Rajagopalan

1984

Hepatology

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The kinetics of dissolution of dispersions of egg phosphatidylcholine (lecithin) by bile salts WBS studied by observing the decrease in turbidity as mixed micelles of lecithin and bile salts were formed. The rate of dissolution of lecithin corresponding to formation of mixed micelles was studied in the presence of dihydroxy bile salts, sodium deoxycholate, sodium chenodeoxycholate, sodium ursodeoxycholate and one trihydroxy bile salt, sodium cholate. The rate of dissolution of lecithin and mixed micelle formation decreased in the order: chenodeoxycholate > deoxycholate cholate > ursodeoxycholate. Kinetic solvent isotope studies in DzO, along with measurement of enthalpies of mixed micelle formation both in HzO and DzO, suggest that formation and stabilization of mixed micelles are related to "hydrophobicity" as estimated by high performance liquid chromatography retention factors.On the basis of phase equilibrium and X-ray diffraction studies, a generally accepted model for the bile saltlecithin mixed micelle was proposed by Small (1, 2) and Dervichian (3). According to this model, a disc-shaped micelle is formed on the association of lecithin with bile salt. The disc core consists of hydrocarbon alkyl chains of the lecithin molecules surrounded by a ring of bile salt molecules. Thus, the disc-shaped micelle exterior presents to the aqueous solvent only the hydrophilic end groups of the lecithin and the hydrophilic sides of the bile salt.Whereas it is generally agreed that mixed micelles occur in these solutions, there remains controversy concerning their detailed structure. Mazer and coworkers (4) have suggested that their quasielastic light scattering data (QLS) can best be interpreted in terms of a mixed disc model. This model preserves the disc-shaped mixed micelle of Small and Dervichian but also requires the presence of some bile salt molecules within the interior of the micelle. These bile salt molecules within the micelle interior are presumed to exist as hydrogen-bonded dimers. Calorimetrically derived exothermic heats of mixed micelle formation have also been interpreted to support this model (5). Recently, Muller (6) has proposed another modification to the mixed micelle model. On the basis of X-ray small angle scattering data, Muller suggests that structural dimorphism exists in bile salt leci- The purpose of this study was to attempt to shed further light on the process of mixed micelle formation by measuring the rate of dissolution of lecithin in bile salt solutions.The kinetics of mixed micelle formation were followed by studying the time-dependent decrease in turbidities of a dispersion of lecithin (L) after addition of a given bile salt (BS) solution (9). In the course of the reaction multilamellar L interacts with BS to form mixed micelles M L + B S e M

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Mechanisms of Dissolution of Human Cholesterol Gallstones

Cited by 44 publications

References 10 publications

Cholesterol monohydrate growth in model bile solutions.

Cholesterol monohydrate growth in model bile solutions.

Accelerating Gallstone Dissolution

Kinetics and Thermodynamics of Dissolution of Lecithin by Bile Salts

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