Biomedical subjects

D Lichtenberg

Publications and source records attributed to D Lichtenberg.

At least 55 records · Page 3Linked to original sources

PubMed1995

Are bilirubin and plasma lipid profiles of premature infants dependent on the lipid emulsion infused?

The effect of a lipid emulsion containing long-chain triglycerides (LCT) and supplemented with L-carnitine on plasma lipids and bilirubin in premature neonates on total parenteral nutrition was compared to that of lipid emulsions containing either LCT or a mixture of LCT and medium-chain triglycerides (MCT). In a double-blind randomized study 49 premature neonates received one of the three fat emulsions, given intravenously, over 16-20 h daily for 6 days. Plasma carnitine levels increased significantly in the supplemented group only; the addition of carnitine did not seem to affect any of the parameters studied. Mean plasma triglycerides rose by 193 and 199% in the carnitine-supplemented and the LCT groups, respectively, and by 314% in the MCT/LCT group. On the sixth day of the study free fatty acids were significantly higher in the MCT/LCT group than in the other two groups. Plasma phospholipids and free cholesterol increased (p < 0.05) progressively in all groups and were correlated (r = 0.74, p < 0.001). At the end of the 6-day study all groups showed a similar decline in free and total bilirubin levels despite the significant increase in plasma lipids and free fatty acids resulting from the stepwise increase in lipid load. No correlation was found between free fatty acids and free bilirubin. Since hyperbilirubinemia and hypertriglyceridemia appear to be clinically independent factors, the infusion of lipids should not be withheld from jaundiced infants on total parenteral nutrition.

Bilirubin↗

PubMed1995

Oxidation of low density lipoprotein upon sequential exposure to copper ions.

Copper-induced LDL oxidation is characterized by an 'induction phase' (lag phase) during which the endogenous antioxidants are consumed, followed by a 'propagation phase' in which the LDL-associated polyunsaturated fatty acids are oxidized. Oxidation products may play an important role in the propagation of the oxidative process in the arterial intima as they increase the permeability of the damaged endothelium to various plasma components, including LDL. We therefore found it of interest to investigate the kinetics of LDL oxidation in vitro under conditions where LDL is sequentially exposed to Cu(2+)-induced oxidation. The results of our studies demonstrate that when native LDL is exposed to copper oxidation in a medium containing oxidized LDL, oxidation of the added LDL may be almost instantaneous. Furthermore, even when native LDL is added to 'oxidizing LDL' towards the end of the lag phase or during the propagation phase it becomes oxidized after a very short lag. This oxidation process, occurring in spite of the possible protective effect of the antioxidants present in the newly added LDL, indicates that although antioxidants prolong the latency period by preventing the formation of active free radicals, when such radicals are present in the system, oxidation propagates. These results lend strong support to the generally accepted paradigm regarding the mechanism of propagation of lipid oxidation. In view of the effect of oxidation products on the permeability of the endothelium, the observed shortening of the lag period may result in a vicious cycle, independent of the LDL-associated antioxidants, leading to continuing oxidation and foam cell formation.

Cations↗

PubMed1995

A new fluorescence method for the continuous determination of surface lipid oxidation in lipoproteins and plasma.

We report on a new method for the determination of lipid oxidation in lipoproteins and plasma. The biological lipid system is preloaded with a fluorescent analog of phosphatidylcholine containing diphenylhexatriene (DPH) propionic acid covalently linked to the sn-2 position. When externally added, the respective phospholipid label (DPHPC) localizes to the surface monolayer of a lipoprotein. Under oxidative conditions (e.g. in the presence of Cu2+ ions) the fluorophore undergoes decomposition, resulting in a continuous decrease of fluorescence intensity which reflects the oxidation of a chemically defined phospholipid molecule with well defined localization. When incorporated into LDL particles, the kinetics of the decrease in DPHPC fluorescence intensity upon exposure to Cu2+ us very similar to that of conjugated diene accumulation. Furthermore, our assay can be applied to follow the oxidation of lipids in diluted serum and may also be developed into a suitable test system for clinical studies of susceptibility of plasma lipids to oxidation.

Diphenylhexatriene↗

PubMed1994

Re-evaluation of the structure of low density lipoproteins.

Low density lipoprotein (LDL) is an established atherogenic factor. Much effort has therefore been devoted to elucidation of its structure, yielding the generally accepted model according to which the neutral lipids (cholesterol ester and triglycerides) form a lipid core emulsified by phospholipids, cholesterol and the amphipathic Apolipoprotein B. Yet, the detailed structure of LDL is not clear. The present work was carried out with the aim of re-evaluating the LDL structure using the minimal number of assumptions: in view of the previously noted surface deficit (lack of sufficient PL and cholesterol to cover the surface of the lipid core) we have assumed that polar head groups are not covered by apo B. Other than that, we have 'allowed' Apo B to penetrate into the PL monolayers and the lipidic core and to pertrude into the solution (be elevated above the PL head group level). We have also 'allowed' neutral lipid penetration into the monolayer and variation of the thickness of the phospholipid monolayers within reasonable boundaries. Based on the established values of relevant constants (molecular weights and volumes, densities and surface areas) we have computed the radius of the particle, the penetration of Apo B into lipidic milieus and the fraction of the surface area covered by Apo B as functions of the LDL composition, the monolayer thickness and the 'elevation' of Apo B above this monolayer. These computations show that at least 40% of the LDL surface must be covered by protein and that the protein penetrates, on the average, only about a half of the PL monolayer. Thus it is not very likely to penetrate into the lipid core. These general features are preserved in the smaller LDL particles of hypertriglyceridemic patients. Assuming that no PL head group is covered by Apo B, the previously described immobilization of 20% of the phospholipids is likely to result from the interaction of Apo B with neighboring PL. According to our computations this can be regarded consistent with the previously proposed arrangement of the apo B as a '3-4 domain structure' or a long string configuration but inconsistent with 'one domain' or 'twenty domain' structures.

Humans↗

PubMed1994

Direct visualization of lipid aggregates in native human bile by light- and cryo-transmission electron-microscopy.

The evolution of microstructures present in human gallbladder and hepatic bile was observed simultaneously by video-enhanced light microscopy (VELM) and transmission electron microscopy of vitrified specimens (cryo-TEM), as a function of time after withdrawal from patients. Fresh centrifuged gallbladder bile samples contained small (6 nm) spherical micelles in coexistence with vesicles (40 nm). Out of the seven bile samples investigated four contained, in addition, two types of elongated aggregates that have not been previously described. Uncentrifuged gallbladder bile also contained a mixture of ribbon- and plate-like crystals seen by VELM, but not by cryo-TEM. In aged (3-6-week-old) gallbladder bile samples VELM also revealed spiral and helical crystal structures. No such crystals were present in hepatic bile samples, although microcrystals, not observable by VELM were seen by cryo-TEM in addition to micelles and vesicles. The similarity of these observations to those observed in bile models lends strong support for the validity of the model systems. Furthermore, the presence of microcrystals in hepatic bile samples, apparently devoid of crystals by light microscopy, indicates that under certain conditions the common criterion of 'nucleation time' (NT), based on light microscopy, does not represent the real time of nucleation. In the human bile samples investigated in this study the dissociation between NT and the time of observation of microcrystals was seen in hepatic but not in gallbladder bile samples. Hence, crystal growth may be rate limiting only in dilute biles.

Bile↗

PubMed1994

The effect of egg yolk on the binding capacity of human spermatozoa to zona pellucida.

OBJECTIVE: To evaluate the effects of Tes and Tris (TEST)-yolk buffer (TYB) incubation on sperm function. DESIGN: Sperm samples obtained from 61 patients attending the infertility clinic were incubated in TYB and control medium. Binding to the zona pellucida (ZP), evaluated by the hemizona assay, membrane functional integrity evaluated by the hypoosmotic swelling test, and acrosome reaction and penetration through cervical mucus were assessed to ascertain the effect of TYB treatment. RESULTS: The only substantial effect of TYB treatment was enhanced sperm binding to the ZP. The mean number of sperm cells attached to the hemizonae with TYB or medium treatment, was 42 +/- 6.1 (+/- SE) and 31 +/- 5.8, respectively (n = 61). However, this improvement was most obvious in 12 patients whose sperm samples exhibited a marked increase in sperm binding capacity following TYB treatment compared to medium without TYB, 71 +/- 5.6 and 12 +/- 2.7, respectively. In the other sperm samples (n = 49), sperm binding capacity was similar following TYB and medium treatment (both 35 +/- 6.0). CONCLUSIONS: A 2-hour incubation of sperm samples with TYB-containing medium (at room temperature) enhances the binding capacity of human spermatozoa in approximately 20% of patients considered to have male factor infertility. The basis of this selective effect has yet to be studied further.

Egg Yolk↗

PubMed1993

Apolipoprotein B exhibits phospholipase A1 and phospholipase A2 activities.

Low density lipoproteins (LDL) as well as isolated apolipoprotein B (ApoB) have been shown to exhibit phospholipase A2 (PLA2) activity toward phospholipids containing an oxidized or short fatty acyl chain at position 2. Some of these studies employed the fluorescent analogue of phosphatidyl choline (PC), C6-NBD-PC, containing NBD-caproic acid (C6-NBD-FA) at position 2 as a substrate, representative of short fatty acyl chains. The release of NBD-caproic acid from position 2 is attributed to PLA2-catalysed hydrolysis. However, this fatty acid can be released also by other enzymatic pathways. In the present study we examined, and ruled out, other enzymatic pathways which may be responsible for the hydrolysis of fatty acids from position 2 of phospholipids. On the other hand, we found that LDL as well as isolated ApoB hydrolyse C6-NBD-FA from both carbon 1 and carbon 2 of these phospholipids, thus exhibiting independent and simultaneous activities of phospholipase A1 and phospholipase A2.

4-Chloro-7-nitrobenzofurazan↗

PubMed1993

Bile and plasma lipid composition in non-obese normolipidemic subjects with and without cholesterol gallstones.

A two-stage study was carried out to characterize the bile and plasma lipid composition in normolipidemic non-obese patients with and without cholesterol gallstones. The first stage involved 11 patients with cholesterol gallstones admitted for elective cholecystectomy and a control group of 16 patients without cholesterol gallstones undergoing elective laparotomy. Bile samples were obtained intraoperatively by aspiration from the gallbladder. The bile of all the gallstone patients was supersaturated with cholesterol and its nucleation time was much shorter than that of bile in the control group (2.5 days vs 22.5 days, respectively, P < 0.001). The biliary fatty acid profile of phosphatidylcholine (PC) and free fatty acids (FFA) of gallstone patients was similar to that of the control group. C-22 fatty acids were found in a higher concentration in the FFA than in the PC fatty acids (P < 0.05) in both groups of patients. Plasma triglyceride levels in the gallstone patients were significantly higher than those in the control group and the biliary cholesterol level correlated with that of plasma triglycerides. In the second stage of the study, plasma lipid profiles were obtained in two additional groups of patients, 20 patients with and 24 patients without cholesterol gallstones, for an in-depth characterization of the differences in plasma lipid profiles. The gallstone patients were found to have not only significantly higher concentrations of plasma triglycerides but increased cholesterol and phospholipid level as well. These differences were essentially due to a higher lipid content of the plasma VLDL fraction, similar to the pattern of patients with type IV hyperlipoproteinemia.

Bile↗

PubMed1992

The use of C6-NBD-PC for assaying phospholipase A2-activity: scope and limitations.

Determination of phospholipase A2 (PLA2) activity is of special interest in view of the abundance of this enzyme in various organelles of all cells, and its role in many cell functions, especially in eicosanoid production. Assaying PLA2 activity is therefore of special importance to cell biology. However, it is a complicated and non-trivial task for several reasons including the critical dependence of PLA2 activity on the physical state of the lipid substrate, the complex kinetics of its action, the low activity of most intercellular and membrane-bound enzymes and the metabolism of the fatty acid products, when applied to intact cell. In recent years the fluorescent analogue of phosphatidylcholine, C6-NBD-PC, has been used for determination of the activity of soluble and membrane-bound PLA2. In the present study we evaluate the use of this method for continuous monitoring of PLA2 activity, based on time-dependent changes in the fluorescence intensity which results from the hydrolysis of C6-NBD-PC into NBD-caproic acid and lysolecithin. The fluorescence intensity of aggregated C6-NBD-PC is reduced due to self-quenching which is maximal in systems containing no additional lipids, when NBD-PC forms micelles. In these systems the hydrolysis increase the fluorescence intensity due to de-quenching, since the NBD caproic acid products dissolves in water in the form of monomers. In contrast, in the presence of additional lipids (mixed micelles, membrane vesicles, lipid emulsion particles or lipoproteins), the probe partitions into lipidic compartments where its fluorescence is only partially quenched (if at all) and its quantum yield is much higher. Consequently, the hydrolysis is accompanied by a decrease in fluorescence. The time course of this change is a complex function of the additional lipid concentration(s) and of physical processes which follow the hydrolysis. Due to this complexity, the assay of PLA2 activity by continuous monitoring of fluorescence is ambiguous. Furthermore, the rate of NBD-PC hydrolysis is very different from that of the 'host' lipid bilayer or monolayer and is less sensitive to the physical state of the lipids. Under various conditions it follows very different kinetics, depending on the ratio of NBD-PC to the host PC. Therefore, it can not be used as a general assay for PLA2 in lipid-containing systems.

Fluorescent Dyes↗

PubMed1992

The effect of short-term lipid infusion on liver function and biliary secretion in rats.

This study was undertaken to determine the effect of various lipid emulsions on the hepato-biliary system in rats. Rats were randomly divided into six groups and infused continuously for 48 hr with either long-chain triglycerides (LCT), medium-chain triglycerides (MCT) or a mixture of MCT and LCT. One group infused with physiological saline solution served as controls. Throughout this period the rats received a fat free diet ad libitum. During the last hour of lipid infusion bile was collected for determination of bile flow and composition. Subsequently, the rats were sacrificed and the morphology and lipid content of the liver determined. Only LCT lipid emulsions induced morphological changes and increased liver cholesterol content. In two rats infused with radiolabeled LCT, no labeled cholesterol was found in the liver, indicating that the excess hepatic cholesterol level may originate from enhanced cholesterol mobilization to the liver. Biliary cholesterol and phospholipid concentrations in LCT-treated rats were also elevated, as was the lithogenic index, whereas the other emulsions had no such effects. None of the emulsions affected the plasma liver function tests or bile flow. We therefore conclude that the lithogenicity of the bile in rats is directly related to the lipid components of the total parenteral nutrition and the type of triglyceride infused.

Animals↗

PubMed1992

Free fatty acids have nucleating effects in model biles.

Nucleating factors are thought to be responsible for the more rapid nucleation of gallbladder bile from patients with gallstones as compared to controls. Biliary proteins and, in particular, mucus and non-mucus glycoproteins are the focus of current research. Non-protein nucleating factors were not extensively investigated. In this study we studied the role of free fatty acids (FFA) as possible nucleating factors. Palmitic, oleic and linoleic acid were added to model biles in increasing concentrations from 0 to 20 mu mol/ml. The nucleation time of model biles decreased to 45%-60% of the initial following the addition of 0.5 to 1 mu mol/ml of each of the three fatty acids. Only a small further decrease in the nucleation time was noted with higher concentrations of up to 20 mu mol/ml. The pronucleating effect of FFA added to whole model bile was also examined in the isolated vesicular and non-vesicular fractions. The decrease in the nucleation time at each concentration of the three fatty acids was in the following order of magnitude: whole bile greater than vesicular phase greater than non-vesicular phase. The addition of each of the three fatty acids resulted in a partial solubilization of vesicles, with transfer of their lipid contents to the non-vesicular fraction. The effect was more marked with oleic acid and least marked with linoleic acid. The vesicular cholesterol to phospholipid ratio did not change following the addition of exogenous free fatty acids. Studies with labeled FFA showed that they migrated with the non-vesicular fraction on gel chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile↗

PubMed1992

Effect of lipid infusion on bile composition and lithogenicity in patients without cholesterol gall stones.

A prospective study was performed to investigate the effect of short term lipid infusion on bile composition and its lithogenicity in humans. Thirty five patients shown to be free of cholesterol gall stones participated in the study. Starting 48 hours before surgery they were infused randomly with a lipid emulsion of either long chain triglycerides (LCT) or a mixture of medium and long chain triglycerides (MCT/LCT) (50%/50%) for six hours each 24 hours. A group of patients infused with a solution of 5% glucose in NaCl 0.9% served as a control. Bile samples were obtained by puncture of the gall bladder during operation. Both lipids caused an increase in biliary cholesterol and phospholipids but this effect was more pronounced and significant (p < 0.001) only with the MCT/LCT emulsion. The fatty acid composition of biliary phospholipids was not affected by either lipid infusion. The cholesterol saturation index increased significantly (p < 0.005) with the MCT/LCT emulsion and there was shortening in the nucleation time but this was not significant. There was no effect on the distribution of cholesterol between micelles and vesicles. This study shows that infusion of MCT/LCT lipid emulsion can cause lithogenic changes in bile composition in humans and may thus contribute to sludge formation and cholelithiasis during long term parenteral nutrition.

Bile↗

PubMed1991

Physico-chemical characterization of Intralipid emulsions.

Fat emulsions containing soy triacylglycerols (100-300 g/l) and egg-yolk phospholipids (12 g/l) are often used for intravenous feeding. Previous studies have shown that these emulsions contain chylomicron-like emulsion particles of diameters of 300-400 nm and excess phospholipids aggregated as vesicles (liposomes), which remain in the infranatant upon floatation of the emulsion particles by ultracentrifugation. This work is devoted to the characterization of the commercial lipid emulsions commonly denoted Intralipids, with special emphasis on the presently ill-defined liposomes. The lipid particles composing commercial lipid emulsions (10%, 20% and 30% Intralipids, Kabivitrum Nutrition) were characterized by the combined use of physical and chemical methods. Each of the emulsions was fractionated by ultracentrifugation in saline into a 'cream' layer which floats to the top of the dispersion upon ultracentrifugation and a relatively transparent infranatant. The cream layer contains large emulsion particles of diameters ranging from 300 to 400 nm, in agreement with theoretical considerations based on their chemical composition as determined by chemical analysis. The infranatants contain about 1 g/l triacylglycerols in addition to phospholipids (from 7.2 g/l in 10% Intralipid to 2.4 g/l in 30% Intralipid) in the form of smaller particles of 70-100 nm diameter. Cryo-transmission electron microscopy shows that the infranatants contain vesicles (mostly unilamellar) at the side of residual small emulsion particles. This conclusion is also consistent with the distribution of phospholipids between outer and inner lamellae, as determined by 31P-NMR.

Fat Emulsions, Intravenous↗

PubMed1990

States of aggregation and phase transformations in mixtures of phosphatidylcholine and octyl glucoside.

The result of mixing varying concentrations of the nonionic detergent octyl glucoside (OG) with small unilamellar vesicles (SUV) of egg phosphatidylcholine (PC) made by sonication depends on the ratio between OG and PC in the mixed aggregates. When this molar ratio (Re) is lower than 1.4, the detergent partitions between the PC vesicles and the aqueous medium with a partition coefficient of K = 0.033 mM-1. As a consequence of introduction of OG into the bilayers, the vesicles grow in size. The resultant vesicles have a mean diameter that is an increasing function of Re and is independent of the total PC concentration. Experiments in which the vesicles were loaded with high molecular weight dextran prior to being exposed to OG suggest that the mechanism responsible for the size growth involves lipid transfer rather than fusion. Mixtures with Re values within the range of 1.4-3.2 separate into two macroscopic phases: The lower phase is clear but very viscous. It contains constant OG and PC concentrations and is characterized by an Re value of 3.2, independent of the composition of the whole dispersion. The upper phase contains vesicles of varying concentrations of OG and PC, but a constant Re of 1.4. When the saturating level of 1.4 OG molecules per PC molecule is approached, the concentration of OG monomers in the aqueous medium reaches the value of 16.6 +/- 0.3 mM, which is the apparent cmc of OG in the lipid-containing medium. OG-PC mixed micelles contain at least 3.2 OG molecules per PC molecule. The mixed micelles present at Re = 3.2 apparently have the shape of oblate ellipsoids with a minor axis of about 2 nm and two major axes of about 25 nm. The surface area of the mixed micelles at this point is just sufficient for them to undergo conversion into the smallest possible spherical vesicles of a radius of 12 nm. At Re values above 3.2, the major axis of the mixed micelles becomes smaller as Re increases, while at values of Re below 3.2 the micelles would have been expected to grow very rapidly with decreasing Re. This may explain the partial vesicle closure occurring below Re = 3.2.

Detergents↗

PubMed1990

Stability of mixed micellar systems made by solubilizing phosphatidylcholine-cholesterol vesicles by bile salts.

Complete solubilization of phosphatidylcholine and cholesterol by bile salts in the form of stable mixed micelles requires that the effective ratio of bile salt/lipids in the mixed micelles (Re = ([bile salt] - critical micellar concentration)/([phosphatidylcholine] + [cholesterol]) will exceed a critical value. This equilibrium solubilizing ratio is an increasing function of the cholesterol/phosphatidylcholine ratio. In contrast, the concentration of sodium cholate required for solubilization of vesicles made of phosphatidylcholine and cholesterol does not increase by increasing the cholesterol/phosphatidylcholine ratio. Consequently, the latter solubilization procedure yields metastable mixed micelles whenever the cholate concentration is higher than that required for vesicle solubilization but lower than that needed for establishing a micellar equilibrium. These metastable mixed micelles undergo partial revesiculation to form cholesterol-rich vesicles that subsequently aggregate. Cholesterol crystallization appears to occur through its reorganization within these aggregated vesicles. The overall rate of the above series of processes increases sharply with the total lipid concentration and with the cholesterol/phosphatidylcholine ratio. The dependence of the rate on the effective ratio of bile salts/lipids is very complex: at any given ratio of cholesterol/phosphatidylcholine within the range of 0.3 to 0.5, increasing the cholesterol/phosphatidylcholine ratio requires higher cholate concentrations for the formation of stable mixed micelles (higher equilibrium solubilizing ratio). On the other hand, the metastable mixed micellar larsystems are long-lived whenever the effective ratio of cholate/lipids is lower than a critical value.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Acids and Salts↗

PubMed1988

Hydrolysis of phosphatidylcholine in phosphatidylcholine-cholate mixtures by porcine pancreatic phospholipase A2.

Pancreatic phospholipase A2 (PLA2)-catalyzed hydrolysis of egg yolk phosphatidylcholine (PC) in mixed PC-cholate systems depends upon composition, structure, and size of the mixed aggregates. The hydrolysis of PC-cholate-mixed micelles made of an equal number of PC and cholate molecules is consistent with a Km of about 1 mM and a turnover number of about 120 s-1. Increasing the cholate/PC ratio in the micelles results in a decreased initial velocity. Hydrolysis of cholate-containing unilamellar vesicles is very sensitive to the ratio of cholate to PC in the vesicles. The hydrolysis of vesicles with an effective cholate/PC ratio greater than 0.27 is similar to that of the mixed micelles. The time course of hydrolysis of vesicles with lower effective ratios is similar to that exhibited by pure dipalmitoyl-phosphatidylcholine (DPPC) large unilamellar vesicles in the thermotropic phase transition region. In the latter two cases, the rate of hydrolysis increases with time until substrate depletion becomes significant. The reaction can be divided phenomenologically into two phases: a latency phase where the amount of product formed is a square function of time (P(t) = At2) and a phase distinguished by a sudden increase in activity. The parameter A, which describes the activation rate of the enzyme during the initial phase in a quantitative fashion, increases with increasing [PLA2], decreasing [PC], decreasing vesicle size, and increasing relative cholate content of the vesicles. The effect of [PLA2] and [PC] on the hydrolysis reaction is similar to that found with pure DPPC unilamellar vesicles in their thermotropic phase transition region. The effect of cholate on the hydrolysis reaction is similar to that of temperature variation within the phase transition of temperature variation within the phase transition of DPPC. These results are consistent with our previously proposed model, which postulates that activation of PLA2 involves dimerization of the enzyme on the substrate surface and that the rate of activation is directly proportional to the magnitude of lipid structural fluctuations. It is suggested that large structural fluctuations, which exist in the pure lipid system in the phase transition range, are introduced into liquid crystalline vesicles by the presence of cholate and thus promote activation of the enzyme.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1988

Effect of calcium on kinetic and structural aspects of dilution-induced micellar to lamellar phase transformation in phosphatidylcholine-cholate mixtures.

Previously, we have shown [Almog, S., Kushnir, T., Nir, S., & Lichtenberg, D. (1986) Biochemistry 25, 2597-2605] that the distribution of cholate between phosphatidylcholine (PC) vesicles and aqueous media apparently obeys a single distribution coefficient, K. In PC-cholate mixed micellar systems, the monomer concentration does not rise much above the cholate's critical micelle concentration (cmc). Consequently, for vesicular systems, the cholate:PC molar ratio in the mixed aggregates (Re) is given by Re = [cholate]/([PC] + 1/K) whereas for mixed micellar systems Re = ([cholate] - cmc)/[PC]. Dilution of mixed micellar systems results in a decrease of Re, due to an increase in the fraction of monomeric PC. If the decrease in Re is to values lower than 0.3, micellar to lamellar transformation occurs. This process involves a sequence of three steps, namely, micellar equilibration followed by vesiculation and subsequent vesicle size growth via a lipid transfer mechanism. The ultimate size of the resultant vesicles is an increasing function of Re. This work is devoted to the effect of calcium on the dilution-induced vesicle formation. Its major findings and conclusions are as follows: (i) Calcium reduces the cmc of the detergent and raises its distribution coefficient between PC vesicles and the aqueous medium. Thus, for any given cholate and PC concentrations, calcium causes an increase of Re. (ii) The rate of all the steps which ultimately lead to an apparent equilibrium vesicle size distribution increases dramatically with increasing calcium concentration. Thus, equilibration is attained in seconds to minutes rather than many hours required in the absence of calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

PubMed1988

Phospholipid peroxidation as a factor in gallstone pathogenesis.

Phospholipid peroxidation markedly reduces the stability of mixed micellar systems composed of cholate, phosphatidylcholine and supersaturating levels of cholesterol. This suggests that lipid peroxidation is likely to play a significant role in the precipitation of cholesterol from gallbladder bile, thus in the pathogenesis of cholesterol gallstones. This conclusion is supported by studies of the nucleation time of cholesterol in gallbladder biles, which was significantly reduced by exposure to a stream of oxygen. This effect of phospholipid peroxidation on cholesterol solubility may occur in other biological fluids as well. In view of the increased lipid peroxidation in the elderly, it may explain the effect of age on the frequency of various diseases related to cholesterol precipitation.

Aging↗