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M C Carey

Publications and source records attributed to M C Carey.

At least 19 recordsLinked to original sources
PubMed1992

Bile salt hydrophobicity controls vesicle secretion rates and transformations in native bile.

After drainage of the bile salt pool, we infused unanesthetized bile fistula prairie dogs (Cynomys ludovicianus) intravenously with taurine-conjugated chenodeoxycholate (TCDC), cholate (TC), ursodeoxycholate (TUDC), and ursocholate (TUC) in concentrations that attained greater than 94% enrichment of biliary bile salts. With decreases in bile salt hydrophobicity, maximum steady state lecithin and to a lesser extent cholesterol secretion rates decreased in the rank order, TCDC greater than TC greater than TUDC greater than TUC. By phase analysis, TCDC-rich and TC-rich biles plotted inside their respective micellar zones, whereas TUDC-rich and TUC-rich biles plotted outside and were so-called "supersaturated" with cholesterol. Quasi-elastic light scattering and electron microscopy, when performed within 30 min of collection, revealed unilamellar vesicles in all biles. By 24 h, vesicles in TCDC-rich and TC-rich biles had dissolved into mixed micelles, whereas vesicles in TUDC-rich biles formed mixed micelles plus multilamellar liquid crystals, and vesicles in TUC-rich biles formed multilamellar liquid crystals exclusively. Because cholesterol/phospholipid molar ratios of multilamellar liquid crystals were less than or equal to 1, cholesterol monohydrate crystals did not form in these biles. We conclude that, despite drastic alterations in bile salt detergency, unilamellar vesicles are the final common pathway for lecithin and cholesterol secretion into bile. During equilibration of bile, the fate of unilamellar vesicles may be micellar, micellar plus liquid crystalline, or liquid crystalline only depending on the detergency (i.e., hydrophobic-hydrophilic balance) of the secreted bile salt.

Absorption↗
PubMed1992

Filamentous, helical, and tubular microstructures during cholesterol crystallization from bile. Evidence that cholesterol does not nucleate classic monohydrate plates.

Precipitation of cholesterol in gallbladder bile is believed to produce platelike cholesterol monohydrate crystals directly. We report complementary time-lapse microscopic studies of cholesterol crystallization from model bile that reveal initial assembly of filamentous cholesterol crystals covered by a monomolecular layer of lecithin. Over a few days, the filaments evolved through needle, helical, and tubular microstructures to form classical platelike cholesterol monohydrate crystals. Similar crystallization phenomena were observed in human gallbladder biles from cholesterol but not pigment stone patients. Synchrotron x-ray diffraction of the earliest filaments suggested a cholesterol monohydrate polymorph or admixture with an anhydrous cholesterol precursor. However, density gradient centrifugation of filamentous crystals revealed that their density was 1.032 g/ml, consistent with anhydrous cholesterol. Conventional x-ray diffraction of transitional crystalline forms was consistent with pure cholesterol monohydrate crystals, as were the equilibrium platelike crystals. These novel findings suggest that crystalline cholesterol in bile may not be completely mature or hydrated initially, but undergoes a series of transformations to become thermodynamically stable monohydrate plates. These observations have important implications for understanding the control of cholesterol crystallization in bile, as well as explaining putative crystal cytotoxicity during gallstone formation.

Bile↗
PubMed1991

Influence of total lipid concentration, bile salt:lecithin ratio, and cholesterol content on inter-mixed micellar/vesicular (non-lecithin-associated) bile salt concentrations in model bile.

We modified classic equilibrium dialysis methodology to correct for dialysant dilution and Donnan effects, and have systematically studied how variations in total lipid concentration, bile salt (taurocholate):lecithin (egg yolk) ratio, and cholesterol content influence inter-mixed micellar/vesicular (non-lecithin-associated) concentrations (IMC) of bile salts (BS) in model bile. To simulate large volumes of dialysant, the total volume (1 ml) of model bile was exchanged nine times during dialysis. When equilibrium was reached, dialysate BS concentrations plateaued, and initial and final BS concentrations in the dialysant were identical. After corrections for Donnan effects, IMC values were appreciably lower than final dialysate BS concentrations. Quasielastic light scattering was used to validate these IMC values by demonstrating that lipid particle sizes and mean scattered light intensities did not vary when model biles were diluted with aqueous BS solutions of the appropriate IMC. Micelles and vesicles were separated from cholesterol-supersaturated model bile, utilizing high performance gel chromatography with an eluant containing the IMC. Upon rechromatography of micelles and vesicles using an identical IMC, there was no net transfer of lipid between micelles and vesicles. To simulate dilution during gel filtration, model biles were diluted with 10 mM Na cholate, the prevailing literature eluant, resulting in net transfer of lipid between micelles and vesicles, the direction of which depended upon total lipid concentration and BS/lecithin ratio. Using the present methodology, we demonstrated that inter-mixed micellar/vesicular concentrations (IMC) values increased strongly (5 to 40 mM) with increases in both bile salt (BS):lecithin ratio and total lipid concentration, whereas variations in cholesterol content had no appreciable effects. For model biles with typical physiological biliary lipid compositions, IMC values exceeded the critical micellar concentration of the pure BS, implying that in cholesterol-supersaturated biles, simple BS micelles coexist with mixed BS/lecithin/cholesterol micelles and cholesterol/lecithin vesicles. We believe that this methodology allows the systematic evaluation of IMC values, with the ultimate aim of accurately separating micellar, vesicular, and potential other cholesterol-carrying particles from native bile.

Bile↗
PubMed1991

Acyl chain unsaturation modulates distribution of lecithin molecular species between mixed micelles and vesicles in model bile. Implications for particle structure and metastable cholesterol solubilities.

We determined the distribution of lecithin molecular species between vesicles and mixed micelles in cholesterol super-saturated model biles (molar taurocholate-lecithin-cholesterol ratio 67:23:10, 3 g/dl, 0.15 M NaCl, pH approximately 6-7) that contained equimolar synthetic lecithin mixtures or egg yolk or soybean lecithins. After apparent equilibration (48 h), biles were fractionated by Superose 6 gel filtration chromatography at 20 degrees C, and lecithin molecular species in the vesicle and mixed micellar fractions were quantified as benzoyl diacylglycerides by high performance liquid chromatography. With binary lecithin mixtures, vesicles were enriched with lecithins containing the most saturated sn-1 or sn-2 chains by as much as 2.4-fold whereas mixed micelles were enriched in the more unsaturated lecithins. Vesicles isolated from model biles composed of egg yolk (primarily sn-1 16:0 and 18:0 acyl chains) or soy bean (mixed saturated and unsaturated sn-1 acyl chains) lecithins were selectively enriched (6.5-76%) in lecithins with saturated sn-1 acyl chains whereas mixed micelles were enriched with lecithins composed of either sn-1 18:1, 18:2, and 18:3 unsaturated or sn-2 20:4, 22:4, and 22:6 polyunsaturated chains. Gel filtration, lipid analysis, and quasielastic light scattering revealed that apparent micellar cholesterol solubilities and metastable vesicle cholesterol/lecithin molar ratios were as much as 60% and 100% higher, respectively, in biles composed of unsaturated lecithins. Acyl chain packing constraints imposed by distinctly different particle geometries most likely explain the asymmetric distribution of lecithin molecular species between vesicles and mixed micelles in model bile as well as the variations in apparent micellar cholesterol solubilities and vesicle cholesterol/lecithin molar ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile↗
PubMed1991

Physical-chemical basis of gallstone formation.

The broad outlines of the physical chemistry of cholesterol solubilization are well understood, but minor components of native biles probably alter the equilibrium solubility of cholesterol in bile and, more importantly, profoundly affect the kinetics of cholesterol crystal formation. The physical chemistry of UCB solubilization is much less clear; two decades after the limits of cholesterol solubilization in bile were reported, we still cannot provide accurate information on the limits of UCB solubility in bile. Although UCB is predominantly solubilized by the same biliary aggregates as cholesterol, the ionic nature of UCB implies that other, quantitatively minor biliary components profoundly alter UCB solubilization. Understanding UCB solubilization in bile and the prevention of black pigment stone formation await further studies. An understanding of the physical chemistry of cholesterol and UCB, both as solubilized in bile and as precipitated in gallstones, is basic to an understanding of the pathogenesis of gallstone disease, as well as current and potential chemical methods of gallstone dissolution and prevention.

Bile Acids and Salts↗
PubMed1990

Physical-chemical behavior of dietary and biliary lipids during intestinal digestion and absorption. 1. Phase behavior and aggregation states of model lipid systems patterned after aqueous duodenal contents of healthy adult human beings.

We developed equilibrium phase diagrams corresponding to aqueous lipid compositions of upper small intestinal contents during lipid digestion and absorption in adult human beings. Ternary lipid systems were composed of a physiological mixture of bile salts (BS), mixed intestinal lipids (MIL), principally partially ionized fatty (oleic) acid (FA) plus racemic monooleylglycerol (MG), and cholesterol (Ch), all at fixed aqueous-electrolyte concentrations, pH, temperature, and pressure. The condensed phase diagram for typical physiological conditions (1 g/dL total lipids, FA:MG molar ratio of 5:1, pH 6.5, 0.15 M Na+ at 37 degrees C) was similar to that of a dilute model bile [BS/lecithin (PL)/Ch] system [Carey, M. C., & Small, D. M. (1978) J. Clin. Invest. 61, 998-1026]. We identified two one-phase zones composed of mixed micelles and lamellar liquid crystals, respectively, and two two-phase zones, one composed of Ch monohydrate crystals and Ch-saturated micelles and the other of physiologic relevance composed of Ch- and MIL-saturated mixed micelles and unilamellar vesicles. A single large three-phase zone in the system was composed of Ch-saturated micelles, Ch monohydrate crystals, and liquid crystals. Micellar phase boundaries for otherwise typical physiological conditions were expanded by increases in total lipid concentration (0.25-5 g/dL), pH (5.5-7.5), and FA:MG molar ratio (5-20:1), resulting in a reduction of the size of the physiological two-phase zone. Mean particle hydrodynamic radii (Rh), measured by quasielastic light scattering (QLS), demonstrated an abrupt increase from micellar (less than 40 A) to micelle plus vesicle sizes (400-700 A) as this two-phase zone was entered. With relative lipid compositions within this zone, unilamellar vesicles formed spontaneously following coprecipitation, and their sizes changed markedly as functions of time, reaching equilibrium values only after 4 days. Further, vesicle Rh values were influenced appreciably by MIL:mixed bile salt (MBS) ratio, pH, total lipid concentration, and FA:MG ratio, but not by Ch content. In comparison, micellar systems equilibrated rapidly, and their Rh values only slightly influenced by physical-chemical variables of physiological importance. In contrast to the BS-PL-Ch system [Mazer, N. A., & Carey, M. C. (1983) Biochemistry 22, 426-442], no divergence in micellar sizes occurred as the micellar phase boundary was approached. The ionization state of FA at simulated "intestinal" pH values (5.5-7.5) in the micellar and physiologic two-phase zones was principally that of 1:1 sodium hydrogen dioleate, an insoluble swelling "acid soap" compound. By phase separation and analysis, tie-lines for the constituent phase in the two-phase zone demonstrated that the mixed micelles were saturated with MIL and Ch and the coexisting vesicles were saturated with MBS, but not with Ch.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Physical-chemical behavior of dietary and biliary lipids during intestinal digestion and absorption. 2. Phase analysis and aggregation states of luminal lipids during duodenal fat digestion in healthy adult human beings.

Following the feeding of a triacylglycerol-rich meal to healthy adult human beings, duodenal contents were aspirated for ex vivo chemical and physical-chemical analyses. The aspirates were collected during established lipid digestion and absorption into a "cocktail" of chemical inhibitors that rapidly inhibited ex vivo lipolysis. Following ultracentrifugation, the lipids separated into a floating oil layer, several interfacial layers, a "clear" or turbid "subphase", and a precipitated "pellet". By chemical and phase analyses, the floating layer was composed of oil-in-water emulsion particles with cores of triacylglycerol (TG), diacylglycerols (DG), and cholesteryl esters (CE) emulsified with a surface coat of partially ionized fatty acids (FA), monoacylglycerols (MG), diacylphosphatidylcholine (PL), and bile salts (BS). The interfacial layers contained similar emulsion particles dispersed among excess emulsifier which adopted a lamellar liquid-crystalline structure. Precipitated pellets were composed principally of emulsifying lipids, with smaller amounts of crystalline calcium soaps and BS. Relative lipid compositions of all but three subphases fell within a two-phase region of the condensed ternary phase diagram (Staggers et al., 1990, companion paper) where saturated mixed micelles composed of BS, FA "acid-soaps", MG, PL, cholesterol (Ch), and traces of DG (and TG) coexisted with unilamellar liquid-crystalline vesicles composed of the same lipids. Attempts to achieve clean separation of vesicles from micelles by repeat ultracentrifugation failed. Compared with the structure and sizes of lipid particles in equilibrated model systems (Staggers et al., 1990), quasielastic light scattering (QLS) analysis revealed that ex vivo micellar sizes (mean hydrodynamic radii, Rh) were similar (less than or equal to 40 A), whereas unilamellar vesicle sizes (Rh = 200-600 A) were appreciably smaller. Two-component QLS analysis of the subphases showed that much larger proportions of lipids were solubilized by micelles than were dispersed as unilamellar vesicles. When followed as functions of time, vesicles frequently dissolved spontaneously into mixed micelles, indicating that, in the nonequilibrium in vivo conditions, the constituent micellar phase was often unsaturated with lipids. These results are consistent with the hypothesis that, during hydrolysis of emulsified DG and TG by luminal lipases, unilamellar vesicles originate in lamellar liquid crystals that form at emulsion-water interfaces in the upper small intestine. In a BS-replete environment, unilamellar vesicles probably represent the primary dispersed product phase of human fat digestion and facilitate the dissolution of lipolytic products into unsaturated mixed micelles.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Rapid (1 hour) high performance gel filtration chromatography resolves coexisting simple micelles, mixed micelles, and vesicles in bile.

We describe the use and validation of Superose 6, a high performance gel filtration medium for rapid, high resolution separation and sizing of coexisting simple micelles, mixed micelles, and vesicles in bile. We fractionated model biles (1.7-4.2 g/dl total lipid concentration, 0.15 M NaCl) composed of lecithin (L), cholesterol (Ch), and the common bile salt taurocholate (TC) using Superose 6 gel filtration columns (1.0 cm diameter, 30 cm length, 0.5 ml model bile application, 1.0 ml fractions) pre-equilibrated and eluted with 2.5-10.0 mM TC. Lipid particle sizes were determined by quasielastic light scattering and lipid compositions by conventional analyses. In the absence of L and Ch, pure TC "biles" (32.2 mM), when eluted in the presence of 7.5 mM TC, yielded a single peak of particles (mean hydrodynamic radii, Rh values of 11-15 A), consistent with simple TC micelles. Model biles containing L and TC ([L] = 13.8 mM, [TC] = 32.2 mM) were fractionated with baseline resolution into TC-L mixed micelles, (Rh values of 30-40 A) and simple TC micelles. In agreement with the ternary TC-L-H2O phase diagram (Mazer, N. A., et al. 1980. Biochemistry. 19: 601-615), the proportions of simple and mixed micelles were inversely related to L concentrations ([L] = 0-32.2 mM) and correlated positively with eluant TC concentration. Superose 6 gel fractionation of model biles "super-saturated" with Ch (TC:L:Ch molar ratio 27:63:10, total lipid concentration 3 g/dl) yielded high resolution separation of vesicles (Rh value of 320 A) from mixed micelles of TC-L-Ch (Rh values of 40-50 A) and simple TC micelles (Rh values of 11-15 A). At an eluant TC concentration of 7.5 mM, Ch-rich vesicles (Ch/L molar ratio = 1.6) separated that contained 40% of total Ch, 9% of total L, and no TC, accurately reflecting predictions of the quaternary L-Ch-TC-H2O metastable phase diagram (Mazer, N. A., and M. C. Carey. 1983 Biochemistry. 22: 426-442). This suggested that a 7.5 mM TC concentration approximated the intermicellar concentration under the experimental conditions. We also fractionated an identical model bile using conventional Sephacryl S-300, a medium generally used to study model and native biles. Compared with Superose 6, the Sephacryl S-300 column of equivalent size yielded particle separations with lower resolution and speed (30 h v l h).(ABSTRACT TRUNCATED AT 400 WORDS)

Bile↗
PubMed1990

Principles of laser light-scattering spectroscopy: applications to the physicochemical study of model and native biles.

We present a nonmathematical treatment of the theoretical and experimental aspects of modern laser light-scattering techniques. We also describe the design of a "home-built" laser light-scattering apparatus used in the authors' laboratory for the physicochemical study of model and native biles. These powerful techniques provide nonperturbing measurements of the sizes, polydispersities and, in suitable cases, concentrations and shapes of simple micelles, mixed micelles, vesicles and large proteins in bile. the sizes of these aggregates (10 to 2,000 A) fall within limits resolvable by laser light and are conventionally expressed as mean hydrodynamic radii, Rh. Static light-scattering measurements of biliary lipid aggregates provide molecular weights and important information concerning particle shape, whereas quasielastic (also referred to as dynamic) light-scattering measurements assess particle sizes and polydispersities. Under favorable circumstances, quasielastic light scattering allows simultaneous determinations of sizes and concentrations of coexisting particle populations. The use of laser light-scattering technology in solving the solution properties and the physicochemical structures of model and native biles is detailed. In view of the extraordinarily diverse backgrounds of researchers in the gallstone field (e.g., internists, surgeons, biochemists, physicists), we believe that the present article (which relies heavily on graphical representations) will afford a better understanding of the usefulness and limitations of laser light-scattering techniques, particularly in their applications to the study of bile.

Bile↗
PubMed1990

Physical chemistry of biliary lipids during bile formation.

Present concepts suggest that the canalicular secretion of bile salts is monomeric, which in turn drives the hepatic secretion of lecithin and cholesterol presumably as unilamellar vesicles into bile. As biliary lipids are concentrated within the biliary tree and gallbladder, bile salts structurally alter lecithin-cholesterol vesicles to form a variety of metastable aggregates whose structures and phase transformations are predicted by phase equilibria considerations. These structural transformations ultimately result in the dispersion of biliary lipids as thermodynamically stable micelles or micelles plus thermodynamically unstable vesicles in common duct and gallbladder biles. The experiments reviewed herein represent experimental simulations of these processes. We used pure aqueous lipid systems to model the putative stages of biliary lipid aggregation on the basis of interactions of small unilamellar vesicles of lecithin-cholesterol with bile salts as the latter's concentrations were varied from below to well above the critical micellar concentration. With submicellar bile salt concentrations likely to be found within hepatocytes, vesicle structures are not appreciably altered. However, perimicellar bile salt concentrations possibly occurring in canaliculi and bile ductules induce the formation of a hexagonal rodlike phase. On further increases in bile salt concentration, the hexagonal rods (formed from lecithin-rich and cholesterol-poor vesicles) are dissolved into mixed micelles as bile salt concentrations exceed their critical micellar concentrations. In slightly cholesterol-"supersaturated" biles, the rapid dissolution of this intermediate phase results in the formation of cholesterol-supersaturated mixed micelles that, in time, give rise to a new population of cholesterol-rich vesicles that coexist with saturated micelles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Chemical species of lipids in bile.

Bile salts, phospholipids and sterols are the major lipid species in bile. The common bile salts possess a steroid nucleus of four fused hydrocarbon rings with polar hydroxyl functions and an aliphatic side chain conjugated in amide linkage with glycine or taurine. Since the ionized carboxylate or sulfonate group on the side chain renders bile salts water soluble, they are formally classified as soluble amphiphiles. The common bile salts differ in the number and orientation of the hydroxyl groups on the steroid nucleus. Bile salts synthesized from cholesterol in the liver are called primary bile salts, which in humans are cholate, with three hydroxyl groups, and chenodeoxycholate, with two hydroxyl groups. Secondary bile salts are created by the action of intestinal bacteria on primary bile salts; deoxycholate, with two hydroxyl groups, and lithocholate, with a single hydroxyl group, are formed from cholate and chenodeoxycholate, respectively. "Tertiary" bile salts are the result of modification of secondary bile salts by intestinal flora or hepatocytes; in humans these are the sulfate ester of lithocholate and ursodeoxycholate, the 7 beta-epimer of chenodeoxycholate. Lecithin (diacylphosphatidylcholine), the major phospholipid in bile, is an insoluble, swelling amphiphile with a hydrophilic, zwitterionic phosphocholine head group and hydrophobic tails comprised of two long fatty acyl chains. Biliary lecithin is derived from the least hydrophobic hepatic lecithins and typically contains a saturated C-16 acyl chain in the sn-1 position and an unsaturated C-18 or C-20 acyl chain in the sn-2 position. Cholesterol, present solely as the nonesterified free alcohol, accounts for more than 90% to 95% of the sterols in bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Separation and quantitation of cholesterol "carriers" in bile.

On the basis of phase equilibria theory and experimental data, we discuss the identity, separation and quantitation of cholesterol-solubilizing lipid aggregates in bile, trivially known as cholesterol "carriers." We first describe analogies (as well as lack of correspondence) between equilibrium phase diagrams of aqueous bile salt, lecithin and cholesterol systems and phase equilibria in native biles. At equilibrium, the possible number and types of different cholesterol "carriers" are limited by constraints placed by the phase rule. These "carriers" include simple micelles (bile salts without lecithin), mixed micelles (bile salts plus lecithin), a lecithin plus cholesterol lamellar phase composed of single bilayer structures (vesicles) or multilamellar structures (liquid crystals) and possibly fragments of a hexagonal phase. Clearly, in this context, cholesterol monohydrate crystals, no matter how small, cannot be considered "carriers." We also use a metastable "phase diagram" for aqueous taurocholate-egg yolk lecithin-cholesterol systems to interpret physicochemical studies on the formation and stability of native biles. In biliary lipid systems, bile salt monomers with or without simple bile salt micelles are present in the aqueous "phase" in equilibrium with mixed micelles/or vesicles. This bile salt concentration is designated the intermicellar concentration but actually represents the total nonmixed micellar/nonvesicular concentration of bile salts (i.e., bile salt monomers and simple bile salt micelles when present) and may be a value that falls below, equal to or above the critical micellar concentration of the bile salts. Experimental estimates of the intermicellar-intervesicular bile salt concentration in model systems are compared with the range of bile salt concentrations that has been used in the literature to separate the presently accepted cholesterol "carriers" (mixed micelles and vesicles) in both model and native biles. We also reinterpret published lipid compositions of phases separated from human bile, using both a nonequilibrium "phase diagram" and an equilibrium phase diagram for the model system, taurocholate-egg yolk lecithin-cholesterol. From these analyses, we conclude that precise quantitation of cholesterol "carriers" in bile awaits methods to accurately determine the intermicellar-intervesicular concentration of bile salts in any individual bile, as well as advances in nonperturbing separatory procedures, and methods to control the thermal and temporal history of native bile samples.

Animals↗
PubMed1990

Structural alterations in lecithin-cholesterol vesicles following interactions with monomeric and micellar bile salts: physical-chemical basis for subselection of biliary lecithin species and aggregative states of biliary lipids during bile formation.

Using complementary physical-chemical methods including turbidimetry, quasielastic light scattering, gel filtration, and phase analysis, we examined the interactions between dilute concentrations of the common bile salt, taurochenodeoxycholate (TCDC), and uni- and multilamellar vesicles (MLVs) composed of defined molecular species of lecithin (L) and varying contents of cholesterol (Ch). Dissolution rates of MLVs with micellar TCDC, as assessed by turbidimetry, were more rapid with vesicles composed of sn-1 palmitoyl species, typical of biliary L, compared with those composed of the more hydrophobic sn-1 stearoyl species. Incorporation of Ch retarded MLV dissolution rates in proportion to the Ch content, and only at high Ch contents were dissolution rates appreciably influenced by the sn-2 fatty acid composition of L. When MLVs contained Ch in amounts characteristic of intracellular membranes (Ch/L approximately 0.1), the dissolution rates of the individual L species by TCDC accurately predicted the steady state L composition of human bile. TCDC interacted with small unilamellar L/Ch vesicles (SUVs) at concentrations well below, as well as appreciably above, its critical micellar concentration. In accordance with the TCDC-egg yolk L-H2O phase diagram, perimicellar concentrations of TCDC interacted with SUVs to form aggregates that were approximately twice the size of the SUVs. These were consistent with the formation of a dispersed hexagonal (rod-like) phase, which co-existed with aqueous bile salt (BS) monomers and either micellar or unilamellar SUV phases. Micellar TCDC completely solubilized SUVs as mixed micelles, putatively via this transient hexagonal phase. With modest Ch-supersaturation, dissolution was followed by the reemergence of a new vesicle population that coexisted metastably with mixed micelles. With high Ch supersaturation, TCDC extracted L and Ch molecules from SUVs in different proportions to form Ch-supersaturated mixed micelles and Ch-enriched SUVs, in accordance with the metastable phase diagram. These experiments are consistent with the hypothesis that sn-1 palmitoyl L species are subselected for bile, in part, by physical-chemical interactions of intracellular BS concentrations with Ch-poor membranes and that the subsequent evolution of Ch-rich vesicles and Ch-saturated mixed micelles occurs via a transitional hexagonal (rod) phase. These liquid-crystalline states are likely to be transient in Ch-unsaturated biles, but may persist in Ch-supersaturated human biles because of their high Ch contents which retard or inhibit these phase transitions.

Bile↗
PubMed1989

Quasielastic light scattering evidence for vesicular secretion of biliary lipids.

We employed quasielastic light scattering, negative-stain, and freeze-fracture electron microscopy to study the time-dependent physicochemical behavior of biliary lipids in fresh rat bile. Three to five minutes after bile collection, the earliest light scattering measurements and electron microscopy revealed unilamellar vesicles (mean hydrodynamic radius, Rh = 430-740 A) coexisting with mixed micelles (Rh = 20-120 A) in all biles. Both percent biliary vesicles (1 to greater than 70%) and micellar sizes varied inversely with bile salt concentration (range 1.6-72 mM) both during endogenous pool drainage and sodium taurocholate infusion. With bile salt concentrations in the vicinity of or below the estimated critical micellar concentration, biliary vesicle concentrations remained constant or increased slightly with passage of time. However, with micellar bile salt concentrations, complete conversion of vesicles to micelles occurred at rates that were directly proportional to bile salt concentration. Back-extrapolation of weighted Rh averages of micelles plus vesicles as functions of time gave sizes of approximately 470 A at 1 min, suggesting the predominance of homogeneously sized unilamellar vesicles at the earliest stages of bile formation. After micellization of lipids, mixed protein aggregates of vesicle size were demonstrated in all biles. These experiments elucidate the dynamic coexistence of lipid vesicles and mixed micelles in cholesterol unsaturated biles and demonstrate that vesicle-to-micelle interconversions of biliary lipid aggregates are normal physiological phenomena within the biliary tree.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Gallstones: an update.

Gallstones are a major health problem in the United States. More than 20 million Americans have gallstones, and a million new cases are discovered each year. A resurgence of interest in this field has been stimulated by advances in understanding the pathogenesis of cholesterol gallstones and in nonsurgical treatments. The purpose of this symposium is to update these advances.

Cholelithiasis↗