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Fatty acid composition of amniotic fluid lecithin and its relationship to amniotic fluid C-peptide in diabetic pregnancy.

Fatty acid composition in lecithin and C-peptide was analysed in amniotic fluid samples obtained from 28 normal and 24 insulin-treated diabetic women in the 34th to 39th week of pregnancy. The pattern of changes of fatty acid composition of amniotic fluid (AF) lecithin was essentially the same in pregnancies complicated by diabetes as in non-diabetic controls. However, at 36/37 weeks, the mean values for palmitoleic acid (16:1) were statistically higher in diabetic women (P less than 0.02), and the mean values for stearic acid (18:0) were higher for normals (P less than 0.02). The mean C-peptide value was more than twice as high (0.71 nmol/l) in the diabetic group than in the control group (P less than 0.01). The lecithin/sphingomyelin (L/S) and palmitic/stearic acid (P/S) ratios were equal in both groups. Neither in five diabetic patients with fetuses indicating marked hyperinsulinism (C-peptide greater than 1.0 nmol/l) nor in the remaining group of patients was there any relationship between C-peptide levels and the lecithin fatty acid composition.

Adult↗

Tetrahydroaminoacridine-lecithin combination treatment in patients with intermediate-stage Alzheimer's disease. Results of a Canadian double-blind, crossover, multicenter study.

We studied the efficacy and safety of oral tetrahydroaminoacridine (THA) combined with lecithin in 52 patients with Alzheimer's disease. The maximal tolerated dose of THA (up to 100 mg per day) was determined during an eight-week titration period, after which the tolerated dose of THA or placebo was given during two sequential randomized periods of treatment lasting eight weeks each. Highly purified lecithin (4.7 g per day) was administered during all phases of the study. Efficacy was expressed in terms of scores on the Mini-Mental State (MMS) test, the modified MMS test, the Hierarchic Dementia Scale, the Rapid Disability Rating Scale-II, and the behavioral scale of Reisberg et al. Safety was assessed by careful clinical monitoring as well as serial measurements of liver aminotransferases. Forty-six patients completed the titration period, and 39 completed the double-blind period, during which only the MMS score showed a small but significant increase (P less than 0.05) after four weeks of treatment with THA. Autonomic side effects of THA were common but mild. Reversible elevations of serum aspartate and alanine aminotransferase levels to three or more times the upper limit of normal occurred in 17 percent of patients; most of the patients affected were women. A liver biopsy performed in one patient showed resolving focal liver-cell necrosis. These studies fail to demonstrate a significant clinical benefit of THA given orally in a maximal dose of 100 mg per day over a period of eight weeks in combination with lecithin.

Administration, Oral↗

Lecithin-cholesterol acyltransferase activity during maturation of human preovulatory follicles with different concentrations of ascorbate, alpha-tocopherol and nitrotyrosine.

The enzyme lecithin-cholesterol acyltransferase (LCAT) transfers an acyl chain from lecithin to cholesterol or oestradiol, thus playing a crucial role in reverse cholesterol transport and follicular synthesis of potent long-lived oestrogens. The mechanism of catalysis is biphasic, as it is based on a phospholipase and an esterifying activity. Sulfhydryl groups were previously reported to be required for the esterification step. Lecithin-cholesterol acyltransferase has previously been shown to be inhibited by thiol oxidants such as peroxynitrite. Peroxynitrite also converts tyrosine to nitrotyrosines. In the present study, high levels of nitrotyrosine associated with low LCAT activity, and vice versa, were found in human preovulatory follicular fluids. Follicular fluids were also analysed for oestradiol (E) and progesterone (P) concentrations. The E/P ratio, which decreases as ovulation approaches, was used to evaluate the maturation status of each follicle. Enzyme activity was negatively correlated with the E/P ratio. Ascorbate (Asc) and alpha-tocopherol (Toc) were titrated in follicular fluid and plasma to evaluate their accumulation or consumption in the follicle. High LCAT activity was found in follicular fluids where Asc and Toc had accumulated, whereas lower activity was associated with Asc and Toc consumption. The consumption of both antioxidants was positively correlated with the E/P ratio. The results suggest that as follicle maturation progresses, Toc and Asc concentrations increase in follicular fluid, thus protecting LCAT from oxidative damage and loss of activity.

Ascorbic Acid↗

Laser Raman investigation of the effect of cholesterol on conformational changes in dipalmitoyl lecithin multilayers.

Large and abrupt changes are observed at 38 degrees C in the 1100 cm(-1) region of the Raman spectrum of aqueous dipalmitoyl lecithin multilayers. They correspond to conformational changes due to the melting of the paraffin side chains. The addition of cholesterol to the multilayers broadens but does not abolish these changes. It is suggested that the addition of cholesterol decreases the interactions between adjacent paraffin side chains of lecithin, causing a change from a cooperative to a noncooperative gel-liquid crystal transition. Removal of water from dipalmitoyl lecithin also results in a noncooperative transition strikingly similar to that caused by addition of cholesterol. Raman spectroscopy thus provides a new and sensitive probe for analyzing the structures of membranes and their constituents.

Chemical Phenomena↗

Translational diffusion coefficient and partition coefficient of a spin-labeled solute in lecithin bilayer membranes.

The translational diffusion coefficient and the partition coefficient of a spin-labeled solute, di-t-butyl nitroxide, in an aqueous suspension of dipalmitoyl lecithin vesicles have been studied by electron spin resonance spectroscopy. When the lecithin is cooled through its phase transition temperature near 41 degrees C, some solute is "frozen out" of the bilayer, and the standard partial molar enthalpy and entropy of partition go more positive by a factor of 8 and 6, respectively. However, the apparent diffusion constant in the lecithin phase is only slightly smaller than that in water, both above and below the transition temperature. The fraction of bilayer volume within which solute is distributed may increase with temperature, contributing to the positive enthalpy of partition. Comparison of time constants suggests that there is a permeability barrier to this solute in the periphery of the bilayer.

Butanes↗

Effects of oral physostigmine and lecithin on memory and attention in closed head-injured patients.

In view of the evidence for the role of the central cholinergic pathways in memory and preliminary studies suggesting alteration of neurotransmitters after severe head injury, we completed a double-blind, placebo-controlled study of combined oral physostigmine and lecithin. Sixteen survivors of moderate to severe closed head injury who had unequivocal memory deficit were studied during the course of inpatient rehabilitation. Although the results generally indicated no difference in the effects of the physostigmine-lecithin combination as compared to lecithin alone, sustained attention on the continuous performance test was more efficient under physostigmine than placebo when the drug condition occurred first in the crossover design. Further investigation of neurotransmitter manipulation is warranted in patients with traumatic brain injury.

Administration, Oral↗

Depression of lecithin-cholesterol acyltransferase esterification in vitamin E-deficient monkeys.

Vitamin E deficiency in two species of monkeys (capuchins and cynamolgus) reduced the in vitro cholesterol esterification by plasma lecithin-cholesterol acyltransferase. The reduction was greates in the most deficient species and in animals fed a diet rich in polyunsaturated fat (safflower oil) stripped of vitamin E. The best correlate of total esterification was the plasma concentration of free cholesterol which reflected the degree of hyperlipidemia, found to be greatest in capuchins fed coconut oil. A logical explanation for the decreased LCAT activity in vitamin E deficiency would be peroxidative damage of substrate (the PUFA of lecithin) or of sulfhydryl sited on lecithin-cholesterol acyltransferase itself. However, neither case was fully supported by the data suggesting that additional information concerning the nature of the reaction and the role of vitamin E is required.

Acyltransferases↗

Release of fatty acids from phosphatidylcholine by lecithin-cholesterol acyltransferase.

Partially purified lecithin-cholesterol acyltransferase [EC 2.3.1.43] from human plasma released fatty acids from phosphatidylcholine. Heating, sulfhydryl reagents, Ca2+, EDTA, and sodium deoxycholate had similar effects on the lecithin-cholesterol acyltransferase and fatty acid releasing activities of the preparation. A specific cofactor protein for lecithin-cholesterol acyltransferase, apoA-1, also enhanced both activities. Release of fatty acid was due to enzymatic hydrolysis of the ester linkage at carbon-2 of phosphatidylcholine. It is suggested that the two activities are due to a single enzyme.

Acyltransferases↗

Baker's asthma related to soybean lecithin exposure.

We report two cases of soybean-lecithin-induced asthma in bakers. The patients experienced clinical symptoms in relation to an occupational exposure to this additive. Skin tests were positive with soybean lecithin, RAST showed a sensitization to soybean, and bronchial challenge tests were positive for a dilution of 10(-3) with this allergen. The same tests remained negative among healthy and asthmatic controls. Soybean lecithin, a common additive in bakery, must be added to the list of numerous aeroallergens involved in baker's asthma.

Adult↗

The effect of parturition on amniotic fluid lecithin concentration.

Amniotic fluid lecithin has been measured during the antenatal period and at comparable periods of gestation at the onset of spontaneous labour. Lecithin values were higher in labour, the difference being statistically significant in two of the three groups studied. Lecithin values were also measured serially during induced labour in 14 normal women at term. A significant fall was observed throughout labour. Creatinine levels were measured in the amniotic fluid in five of these patients and showed no significant change.

Amniocentesis↗

Effect of surfactant monomers on chloramphenicol association to an albumin-lecithin complex: a model for modified drug absorption.

The binding of chloramphenicol to an albumin-lecithin complex in the presence or absence of premicellar concentrations of both ionic and non-ionic surfactants has been examined. Long chain, strong ionic detergents, such as sodium dodecyl sulphate or cetyltrimethylammonium bromide, severely perturb protein structure and eventually allow full separation of the complex into lecithin and albumin-detergent complexes. The dissociation process is reversible upon the removal of the detergent by exhaustive dialysis. After the splitting of the complex, the amount of antibiotic associated with the lipid-protein mixture increases. Structural alteration of the albumin-lecithin complex and the increase in the binding of chloramphenicol have an effect on the transfer rate of this antibiotic across an artificial barrier consisting of an aqueous dispersion of the same complex, as observed in a model system. It is suggested that a reversible alteration in membrane structure, and consequently in membrane permeability, might be easily effected, at the molecular level, through a reversible dissociation of structural lipoproteins into their components, operated by premicellar concentrations of ionic surfactants. This represents a tentative picture of the possible events taking place within the membrane and modifying the absorption rate of a drug, when it is associated with surfactants in a pharmaceutical preparation.

Absorption↗

Pseudo-ternary phase diagrams of lecithin-based microemulsions: influence of monoalkylphosphates.

The formation of macroscopically homogeneous, stable, fluid, optically transparent, isotropic solutions (microemulsions) was delineated, at 25 degrees C, for systems containing water, soybean lecithin, sodium monoalkylphosphate (hexyl or ocytl), alcohol and isopropyl myristate. Six straight or branched alcohols (1-butanol, 2-butanol, isobutanol, 1-pentanol, 2-pentanol, 3-pentanol) were investigated as co-surfactants. A constant lecithin/alcohol mixing ratio was used, while the aqueous phase consisted of a solution of alkylphosphates at different concentrations. An increase of the microemulsion domain was seen by increasing the concentration of the alkylphosphate. With 0.2m hexylphosphate, as aqueous phase, the microemulsion domain consisted of a single, region, that, in the presence of butylic alcohols, spanded the greater portion of the phase diagram. In the presence of amyl alcohols the area of this region was much smaller. With 0.2 m octylphosphate the realm of existence of the microemulsions, except for 1-pentanol, consisted of two regions separated by a liquid-crystal region. With all the alcohols examined, the liquid-crystal phase solubilized a larger amount of oil in the presence of octylphosphate than in the presence of hexylphosphate. The stability ranges of microemulsions in systems containing soybean, lecithin, alcohol, water, and isopropyl myristate can be greatly increased by using a second hydrophobic amphiphile, such as hexylphosphate, to adjust the hydrophilic-lipophilic balance or the spontaneous peaking properties of lecithin-alcohol systems.

Chemistry, Pharmaceutical↗

Cholesterol dissolution rate in micellar bile acid solutions: retarding effect of added lecithin.

In vitro studies on the dissolution rate of cholesterol monohydrate crystals in micellar bile acid solutions showed that the addition of lecithin decreases the dissolution rate even though lecithin increases the equilibrium solubility of cholesterol in these solutions. The reduction in rates caused by lecithin was attributed to a large crystal-solution interfacial barrier. An effective permeability coefficient for the interfacial barrier was calculated to be around 1.5 x 10(-5) centimeter per second for the transport of cholesterol molecules.

Bile Acids and Salts↗

Induction of choline phosphotransferase and lecithin synthesis in the fetal lung by corticosteroids.

Rabbit fetuses 23 to 24 days of gestation were injected with either 9-fluoroprednisolone acetate or saline. Three days later the lungs of steroid-treated animals showed a significant increase in lecithin concentration and cholinephosphotransferase activity. In addition, lung slices from these animals incorporated more [(14)C]choline into lecithin. The rise in enzyme activity and [(14)C]choline incorporation was blocked by prior treatment of fetuses with cycloheximide but not by treatment with actinomycin D. It is proposed that the corticosteroids induce de novo synthesis of the lung enzyme, which in turn leads to increased synthesis of lecithin through the choline incorporation pathway. Furthermore, it appears that the site of regulation involves translation of messenger RNA.

Animals↗

Lecithin agar for detection of microbial phospholipases.

Lecithin agar was developed on which phospholipase C produced turbid zones and phospholipase A produced clear zones. Reactions on lecithin agar agreed 74% of the time with reactions in egg yolk broth. On lecithin agar, interpretation was easier, phospholipase A was detectable, and opaque zones were visible 1 or 2 days earlier than on egg yolk agar. All constituents of the medium can be autoclaved.

Agar↗

Use of synthetic cardiolipin and lecithin in the antigen used by the venereal disease research laboratory test for serodiagnosis of syphilis.

The Venereal Disease Research Laboratory (VDRL) test is a microflocculation test for syphilis that uses an antigen containing cardiolipin, lecithin, and cholesterol. For more than 50 years, the preparation of natural cardiolipin and lecithin for this test has been based on the Pangborn method which involves isolating and purifying these components from beef hearts. This process is tedious and time-consuming and results in a variable purity range. In our studies, we found that a VDRL antigen using synthetic tetramyristoyl cardiolipin and synthetic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (lecithin) was as specific in detecting syphilis as a VDRL antigen made with natural components. In 85% of the cases, we obtained an endpoint titer of 1/2 or 1 dilution more than a titer obtained with a VDRL antigen made with natural components. The use of these pure synthetic compounds, with a purity of 99%, would offer advantages in the standardization and stability of the VDRL antigen. Because this antigen is the basic ingredient in the preparation of nontreponemal reagents such as the rapid plasma reagin, toluidine red unheated serum test, and the unheated serum reagin, the use of this synthetic VDRL antigen should also increase the reactivity of these reagents.

Cardiolipins↗

Efficacy of tacrine and lecithin in mild to moderate Alzheimer's disease: double blind trial.

OBJECTIVE: To assess the efficacy of tacrine and lecithin in treating Alzheimer's disease over nine months. DESIGN: Double blind randomised controlled trial. SETTING: Outpatients clinic of university department of geriatric medicine. SUBJECTS: 53 subjects (26 women, 27 men) with probable Alzheimer's disease. 41 completed the dose finding phase and were randomised to treatment. 32 (14 tacrine, 18 placebo) completed nine months' treatment. INTERVENTIONS: Lecithin and tacrine or lecithin and placebo for 36 weeks. MAIN OUTCOME MEASURES: Scores on neuropsychological tests sensitive to deficits in the cholinergic system; mini-mental state score; behaviour change; mood; functional state; and stress in carers. RESULTS: The tacrine and placebo groups were similar except that the tacrine group had a longer duration of disease (mean 5.4 v 2.5 years in placebo group; P = 0.003). Only 17 of the 32 patients could tolerate the maximum dose of tacrine (100 mg). No significant difference was found between the groups for any of the tests after nine months' treatment except for the digit backwards test, which is insensitive to cholinergic deficit. Analysis of subjects taking the maximum dose of tacrine and of subjects with mild dementia also found no differences. CONCLUSIONS: Tacrine produces no clinically relevant improvement over 36 weeks at the doses tolerated by these patients.

Activities of Daily Living↗

Rapid enzyme analysis of amniotic fluid phospholipids containing choline: a comparison with the lecithin to sphingomyelin ratio in prenatal assessment of fetal lung maturity.

The relation between the choline containing surfactant phospholipids lecithin and sphingomyelin in amniotic fluid and fetal lung maturity is well established. An enzymatic method that had been automated and optimised for use on a centrifugal analyser was used to measure the total choline containing phospholipids in amniotic fluid. The total time taken for this assay was 10 minutes. The results obtained from 100 patient samples, using this procedure, compared favourably with the results obtained by the thin layer chromatography procedure used to determine the lecithin to sphingomyelin ratio (r = 0.93). A clinical study of 60 patients showed that this assay predicted prenatal respiratory distress syndrome as well as the lecithin to sphingomyelin ratios. The advantage of this assay over existing procedures is that it requires minimum preparation of the specimen and no extraction, is quick, and shows a high degree of precision.

Amniotic Fluid↗