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Abstracts

Abstracts

Alzheimer's (Phosphatidylserine)

Alzheimer's

Patients with probable Alzheimer's disease (#70) were randomly allocated to groups: one taking phosphatidylserine 2 x 200 mg/day.

Patients underwent neuropsychological testing as well as measurement of the regional cerebral metabolic rate for glucose using positron emission tomography (PET).

Indicated that phosphatidylserine treatment has an effect on different measures of brain function. Since neuropsychological improvements were best documented after 8 and 16 weeks and faded towards the end of the treatment period, it must be concluded that this symptomatic therapy is mainly of short-term benefit and was overcome by the progressive pathological changes at the end of the treatment period.

Long-term effects of phosphatidylserine, pyritinol, and cognitive training in Alzheimer's disease. A neuropsychological, EEG, and PET investigation. Heiss-WD; Kessler-J; Mielke-R; Szelies-B; Herholz-K. Dementia. 1994 Mar-Apr; 5(2): 88-98.

After the treatment period the group with cognitive training + phosphatidylserine showed a significant glucose enhancement and improved cognitive functioning compared to the other groups.

Activation PET as an instrument to determine therapeutic efficacy in Alzheimer's disease. Heiss-WD; Kessler-J; Slansky-I; Mielke-R; Szelies-B; Herholz-K. Ann-N-Y-Acad-Sci. 1993 Sep 24; 695: 327-31.

Amyloid beta protein (A beta P) is the 40-42 residue polypeptide implicated in the pathogenesis of Alzheimer's disease (AD).

Suggest that the ion channel activity of the polypeptide may be the basis of its neurotoxic effects.

A new hypothesis for the mechanism of amyloid toxicity, based on the calcium channel activity of amyloid beta protein (A beta P) in phospholipid bilayer membranes. Pollard-HB; Rojas-E; Arispe-N. Ann-N-Y-Acad-Sci. 1993 Sep 24; 695: 165-8.

Asymmetry

Asymmetry

The endogenous phosphatidylserine of normal erythrocytes is confined to the cytoplasmic leaflet of the membrane. However, under pathologic conditions transmembrane asymmetry can be altered and cytofacial phosphatidylserine may appear on the cell surface.

Protein kinase C activation affords a sensitive and specific measure of phosphatidylserine in the outer monolayer of biological membranes.

Protein kinase C as a measure of transbilayer phosphatidylserine asymmetry. Daleke-DL; Huestis-WH; Newton-AC. Anal-Biochem. 1994 Feb 15; 217(1): 33-40.

Phospholipid topology in human brain tumor microsomes was investigated.

In non-neoplastic brain cortex and white matter the outer leaflet of the bilayer contains predominantly phosphatidylcholine and the inner leaflet mostly phosphatidylethanolamine and phosphatidylserine. Sphingomyelin is equally distributed between the two leaflets. In microsomes from glioma and meningioma tumors, a significant decrease in phosphatidylcholine and sphingomyelin at the outer surface was observed.

Phospholipid asymmetry in microsomal membranes of human brain tumors. Ledwozyw-A; Lutnicki-K. Acta-Physiol-Hung. 1993; 81(1): 37-43.

Autoantibodies (Phosphatidylserine)

Autoantibodies

Selective immunoglobulin A (IgA) deficiency (sIgAD) is associated with certain autoimmune states. Increased production of autoantibodies and eventual development of overt autoimmune disease are related in part to genetic and environmental factors as well as to the immune deficiency.

Surveyed serum specimens from healthy subjects (#60) with sIgAD for the presence of 21 different autoantibodies by enzyme-linked immunosorbent assays.

The frequencies of 16 autoantibodies were higher in sIgAD patients than in normal healthy controls. e.g. phosphatidylserine (20%),

This supports the notion of polyclonal stimulation by repeated environmental stimuli as an etiologic mechanism. Alternatively, the increased frequency may be caused by a dysregulation of the immune response in such individuals.

The mere detection of autoantibodies cannot predict whether a subject with sIgAD will develop an autoimmune disease or determine which specific disease will emerge.

Multireactive pattern of serum autoantibodies in asymptomatic individuals with immunoglobulin A deficiency. Barka-N; Shen-GQ; Shoenfeld-Y; Alosachie-IJ; Gershwin-ME; Reyes-H; Peter-JB. Clin-Diagn-Lab-Immunol. 1995 Jul; 2(4): 469-72.

Antiphospholipid antibodies (aPLs) are associated with pregnancy loss, pregnancy-induced hypertension, and intrauterine growth retardation. Phosphatidylserine (PS)-dependent antigens are expressed in formalin-fixed cells concurrent with differentiation in a choriocarcinoma model (BeWo) of cytotrophoblast.

A PS-dependent antigen is expressed on the surface of a model of differentiating cytotrophoblastic cells and should be accessible in vivo to circulating aPLs.

Expression of phosphatidylserine-dependent antigens on the surface of differentiating BeWo human choriocarcinoma cells. Rote-NS; Chang-J; Katsuragawa-H; Ng-AK; Lyden-TW; Mori-T. Am-J-Reprod-Immunol. 1995 Jan; 33(1): 114-21.

Diverse immunologic abnormalities have been described in women who received silicone breast implants.

Chief complaints included: polyarthralgias, fatigue, myalgias, morning stiffness, and decreased memory. All 250 sera were tested blindly using a panel of 20 autoantigens including: phosphatidylserine (PS), myeloperoxidase (MPO), sulfatides (sulf), and thyroglobulin (TG).

Values from individual patients were considered positive only when greater than 3 SD above the control mean. There was a significant greater frequency of autoantibodies in women with implants for 15 of the 20 autoantigens; these were particularly striking for e.g. PS. Many patients harbored several autoantibodies; 20% had four autoantibodies; 8% had six autoantibodies. The association of autoantibodies and implants suggests an adjuvant action of silicon/silicone byproducts.

Multiple autoantibodies in patients with silicone breast implants. Bar-Meir-E; Teuber-SS; Lin-HC; Alosacie-I; Goddard-G; Terybery-J; Barka-N; Shen-B; Peter-JB; Blank-M; et-al. J-Autoimmun. 1995 Apr; 8(2): 267-77.

Paired serum and cerebrospinal fluid (CSF) samples from 70 patients with inflammatory and non-inflammatory neurological diseases, as well as 10 sera from patients with primary antiphospholipid syndrome (PAS), six of which presented with cerebrovascular ischemic syndromes, were studied for the presence of anticardiolipin antibodies (ACA) of the G and M classes. PAS sera and some selected paired CSF and serum specimens, were also analyzed for the presence of anti-phosphatidylserine (PS) and anti-phosphatidylethanolamine (PE) antibodies. High levels of IgG and IgM ACA were synthesized intrathecally only in patients with neurosyphilis. Patients with other infectious or inflammatory neurological diseases very rarely showed detectable levels of ACA in serum and/or CSF. ACA were found not only in patients with untreated PAS but also in the serum of 3/7 patients with migraine, thus confirming a relationship between ACA and vascular disorders.

The search for PS and PE antibodies disclosed that in PAS patients the serum titers of these antibodies mirrored ACA IgG and IgM titers, while they were never found in the CSF.

Cerebrovascular and neurological disorders associated with antiphospholipid antibodies in CSF and serum. Gallo-P; Sivieri-S; Ferrarini-AM; Giometto-B; Ruffatti-A; Ritter-E; Chizzolini-C; Tavolato-B. J-Neurol-Sci. 1994 Mar; 122(1): 97-101.

Recent studies have suggested that the lupus anticoagulant (LA) may be specific for prothrombin, prothrombin-phospholipid complexes, or beta 2 glycoprotein 1 (beta 2GP1) rather than phospholipids.

Determine whether LA is indeed phospholipid specific. IgG with LA activity was absorbed by negatively charged but not by zwitterionic phospholipids. In like manner, PS, CL and PS/PC, but not PC liposomes, absorbed IgG with aCL activity.

At least one population of antibodies with LA activity is phospholipid specific.

Are immunoglobulins with lupus anticoagulant activity specific for phospholipids? Pierangeli-SS; Harris-EN; Gharavi-AE; Goldsmith-G; Branch-DW; Dean-WL. Br-J-Haematol. 1993 Sep; 85(1): 124-32.

Beta-thalassemia

Beta-thalassemia

Investigation of red blood cells from beta-thalassemia patients by means of prothrombinase assay reveals phosphatidylserine in the outer leaflet of the plasma membrane. This might explain their elevated susceptibility to phagocytosis by macrophages and the chronic hypercoagulable state, frequent thrombotic events, and life-long platelet activation that are found in thalassemic patients.

Phosphatidylserine in the outer leaflet of red blood cells from beta-thalassemia patients may explain the chronic hypercoagulable state and thrombotic episodes. Borenstain-Ben-Yashar-V; Barenholz-Y; Hy-Am-E; Rachmilewitz-EA; Eldor-A. Am-J-Hematol. 1993 Sep; 44(1): 63-5.

Bile

Bile

Much research in the pathophysiology of gall stones has been devoted to various molecular species of bile salts. Recent findings have shown the importance of phospholipids in biliary pathophysiology.

The addition of increasing doses of egg lecithin to human and model biles progressively prolonged the nucleation time. Concurrently biliary cholesterol was shifted from the vesicular to the non-vesicular carrier(s) while the cholesterol/phospholipid ratio of the remaining vesicles was progressively lowered.

Phosphatidylserine shifted most of the cholesterol to the non-vesicular carrier(s).

Findings show the importance of phospholipid species in biliary pathophysiology and may be useful when trying to manipulate cholesterol carriers and solubility in bile.

Effect of phospholipids and their molecular species on cholesterol solubility and nucleation in human and model biles. Halpern-Z; Moshkowitz-M; Laufer-H; Peled-Y; Gilat-T. Gut. 1993 Jan; 34(1): 110-5.

Epilepsy (Phosphatidylserine)

Epilepsy

Previous experimental studies have shown that the simultaneous administration of gamma-aminobutyric acid (GABA) and phosphatidylserine (PS) can exert an anticonvulsant activity in different seizure models; moreover, a preliminary trial showed some effect of the association GABA-PS in patients with absence seizures.

This study investigated the antiepileptic properties of GABA-PS in the model of human photosensitivity. Patients (#9) with epilepsy associated with an EEG pattern of photoconvulsive response at intermittent photic stimulation. The photosensitivity range (PSR) was determined at hourly intervals both in basal conditions and after the administration of a single oral dose of GABA (3000 mg) and PS (600 or 1200 mg). The administration of GABA-PS was not associated with any systematic changes of PSR, nor with any significant differences of time course profiles on each daily session. No correlation was found between PSR percent deviations from baseline and GABA serum levels. These results indicate that a single acute administration of GABA-PS has no effect in the human photosensitivity model, and suggest that the efficacy of GABA-PS in human epilepsy may possibly require chronic administration.

GABA and phosphatidylserine in human photosensitivity: a pilot study. Cocito-L; Bianchetti-A; Bossi-L; Giberti-L; Loeb-C. Epilepsy-Res. 1994 Jan; 17(1): 49-53.

Exercise (Phosphatidylserine)

Exercise

The effects were investigated of physical training and exercise on lipids of the erythrocyte membrane of healthy students.

Physically trained students had similar physical characteristics to control students but a significantly higher aerobic capacity, estimated as the maximal oxygen uptake and anaerobic threshold. Of the phospholipids examined, only the content of membrane phosphatidylserine was significantly lower in the trained group. Fatty acid analysis showed that the amount of docosahexaenoic acid in membrane phosphatidylserine was lower in the trained group.

Maximal exercise decreased membrane phosphatidylserine in the control group but not in the trained group. It also significantly decreased the relative amounts of unsaturated fatty acids in both phosphatidylcholine and phosphatidylserine in the untrained group. Maximal oxygen uptake was negatively correlated with the amount of erythrocyte membrane phosphatidylserine. These results would indicate that both physical training and acute exercise decrease phosphatidylserine and polyunsaturated fatty acids in erythrocyte membranes, possibly due to lipid peroxidation, suggesting limited enhancement of erythrocyte defense mechanisms in adaptation to chronic oxidative stress.

Changes in erythrocyte membrane phospholipid composition induced by physical training and physical exercise. Sumikawa-K; Mu-Z; Inoue-T; Okochi-T; Yoshida-T; Adachi-K. Eur-J-Appl-Physiol. 1993; 67(2): 132-7.


Glycerobackbone

Glycerobackbone

Both the D- and L-isomers of phosphatidylcholine, phosphatidylglycerol, phosphatidic acid, and phosphatidylserine have approximately equal antiviral activity.

Antiviral phospholipids. Anti-HIV drugs conjugated to the glycerobackbone of phospholipids. Pidgeon-C; Markovich-RJ; Liu-MD; Holzer-TJ; Novak-RM; Keyer-KA. J-Biol-Chem. 1993 Apr 15; 268(11): 7773-8.

HDL

HDL

The appearance of anionic lipids on the extracellular surface of cells is required for the formation of the procoagulant complex that leads to the activation of prothrombin.

Procoagulant activity would be expected to be inhibited by substances that stabilize the membrane structure and hence inhibit the transbilayer diffusion of phosphatidylserine from the cytoplasmic to the extracellular surface of the plasma membrane.

Procoagulant activity in human erythrocytes is inhibited by high-density lipoprotein (HDL). This may contribute to the protective role of HDL against arteriosclerosis and thrombosis.

HDL and apolipoprotein A-I protect erythrocytes against the generation of procoagulant activity. Epand-RM; Stafford-A; Leon-B; Lock-PE; Tytler-EM; Segrest-JP; Anantharamaiah-GM. Arterioscler-Thromb. 1994 Nov; 14(11): 1775-83.

Influenza

Influenza

To study the role of the target membrane in influenza virus fusion we chose erythrocyte membranes whose phospholipid arrangement can readily be modified. The phospholipids of normal erythrocytes are arranged asymmetrically across the plasma membrane; phosphatidylcholine (PC) and sphingomyelin are predominantly on the outer surface, whereas others such as phosphatidylserine (PS) and phosphatidylethanolamine (PE) are predominantly restricted to the inner leaflet. However, erythrocytes can be lyzed and resealed under conditions where the asymmetric distribution of

Effects on influenza virus fusion are not associated with any particular phospholipid headgroup, but rather related to the packing characteristics of the target membrane.

Role of target membrane structure in fusion with influenza virus: effect of modulating erythrocyte transbilayer phospholipid distribution. Herrmann-A; Clague-MJ; Blumenthal-R. Membr-Biochem. 1993 Jan-Mar; 10(1): 3-15.

Lupus (Phosphatidylserine)

Lupus

The specificity and immunoglobulin isotype distribution of antiphospholipid (aPL) antibodies have been evaluated in patients (#68) with systemic lupus erythematosus (SLE) by ELISA.
(72%) were positive for aPL antibodies of different isotypes and directed to one or more PL epitopes e.g. phosphatidylserine (PS, 35%).

Prevalence and clinical significance of antiphospholipid antibodies to noncardiolipin antigens in systemic lupus erythematosus. Toschi-V; Motta-A; Castelli-C; Gibelli-S; Cimminiello-C; Molaro-GL; Gibelli-A. Haemostasis. 1993 Sep-Oct; 23(5): 275-83.

Membrane binding of factor

Membrane binding of factor

Phosphatidylserine, a negatively charged lipid, is exposed on the platelet membrane following cell stimulation, correlating with the expression of factor VIII receptors. We have explored the importance of the negative electrostatic potential of phosphatidylserine vs chemical moieties of phosphatidylserine for specific membrane binding of factor VIII.

The soluble phosphatidylserine moiety, O-phospho-L-serine, inhibited factor VIII binding to phosphatidylserine-containing membranes with a Ki of 20 mM, but the stereoisomer, O-phospho-D-serine, was 5-fold less effective. Furthermore, binding of factor VIII to membranes containing synthetic phosphatidyl-D-serine was 5-fold less than binding to membranes containing phosphatidyl-L-serine. Membranes containing synthetic phosphatidyl-L-homoserine, differing from phosphatidylserine by a single methylene, supported high-affinity binding, but it was not specific as factor VIII was displaced by other plasma proteins. O.

Results indicate that membrane binding of factor VIII is mediated by a stereoselective recognition O-phospho-L-serine of phosphatidylserine and that negative electrostatic potential is of lesser importance.

Specific membrane binding of factor VIII is mediated by O-phospho-L-serine, a moiety of phosphatidylserine. Gilbert-GE; Drinkwater-D. Biochemistry. 1993 Sep 21; 32(37): 9577-85.

Psychosis

Psychosis

Contents of plasma membrane major phospholipids, cholesterol, and cholesteryl esters of fibroblasts from drug-naive psychotic patients were compared with those from normal controls.

Contents of total phospholipids as well as phosphatidylserine, phosphatidylinositol and phosphatidylethanolamine were significantly lower in fibroblasts from patients than in those from normal controls

Data support the hypothesis that schizophrenia is associated with disordered membrane lipid metabolism, and that this predates the onset of psychosis.

Plasma membrane phospholipid and cholesterol distribution of skin fibroblasts from drug-naive patients at the onset of psychosis. Mahadik-SP; Mukherjee-S; Correnti-EE; Kelkar-HS; Wakade-CG; Costa-RM; Scheffer-R. Schizophr-Res. 1994 Oct; 13(3): 239-47.

T-cells

T-cells

Phosphatidylserines inhibit mitogen-induced T cell activation. This inhibitory action requires a protein present in bovine and human serum. Partial purification and phospholipase assay show that this protein has phospholipase A activity on phosphatidylserine but not phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol.

The unsaturated fatty acid is mainly responsible for the PS-induced inhibition and that 2-acyl lysophosphatidylserine enhances the inhibitory effect of fatty acid.

Role of a serum phospholipase A1 in the phosphatidylserine-induced T cell inhibition. Bellini-F; Bruni-A. FEBS-Lett. 1993 Jan 18; 316(1): 1-4.

Cognitive Dysfunction Disorders

Cognitive dysfunction disorders

Phosphatidylserine (PS) may improve cognitive function in cognitive dysfunction disorders, especially dementia. As substantiated in clinical trials, PS may improve memory, learning, concentration, word recall, and mood in middle-aged and elderly patients with dementia or age-related cognitive disorder.

Kidd PM: A review of nutrients and botanicals in the integrative management of cognitive dysfunction, Altern Med Rev 1999 Jun; 4(3): 144-61

Alcoholic Liver Disease

Alcoholic "Liver" Disease

"Alcoholic" liver injury has been reported to be directed preferentially against the "proteins" of the "cell" membrane, sparing the "phospholipids". However, antiphospholipid antibodies against certain cell membrane phospholipids are known to be associated with a variety of diseases.

Determine whether "serum" antibodies were generated against the following membrane phospholipids: phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol (cardiolipin) and phosphatidic acid.

Antiphospholipid antibodies in alcoholic patients seem to reflect disease progression and correlate significantly with disease severity.

"Phospholipid" antibodies in alcoholic "liver disease". Chedid-A; Chadalawada-KR; Morgan-TR; Moritz-TE; Mendenhall-CL; Hammond-JB; Emblad-PW; Cifuentes-DC; Kwak-JW; Gilman-Sachs-A; et-al. Hepatology. 1994 Dec; 20(6): 1465-71.

Cell Age

Cell Age

Human red blood cells ("RBC") were separated by density. Cell "age" is related to cell density and that cells of increasing age and density display higher amounts of PS in their outer leaflet.

Exposure of phosphatidylserine in the outer leaflet of human red blood cells. Relationship to cell density, cell age, and clearance by mononuclear cells. Connor-J; Pak-CC; Schroit-AJ. J-Biol-Chem. 1994 Jan 28; 269(4): 2399-404.

Cisplatin-PS Complex

Cisplatin-PS Complex

This study indicates that the anti-cancer drug cisplatin may not form a toxic complex with phosphatidylserine (PS). In a clinical study, cisplatin-PS interaction in human erythrocytes and tumor cell lines were observed. A cisplatin-PS complex was found in lysed cells due to prolonged storage or hypotonic shock. However, such a complex was not found in intact tumor cells. The outcome of this experiment indicated that the cisplatin-PS mixture might not enhance the cytoxicity of the cisplatin.

Burger KN, Staffhorst RW, De Kruijff B: Interaction of the anti-cancer drug cisplatin with phosphatidylserine in intact and semi-intact cells, Biochim Biophys Acta 1999 Jun 9; 1419(1): 43-54

Cognitive Decline (Phosphatidylserine)

Cognitive Decline

Assess the therapeutic efficacy and the safety of oral treatment with phosphatidylserine (BC-PS) vs placebo in a group of geriatric patients with cognitive impairment (Northeastern Italy).

The efficacy of treatment compared to placebo was measured on the basis of changes occurring in behavior and cognitive performance using the Plutchik Geriatric Rating Scale and the Buschke Selective Reminding Test. Statistically significant improvements in the phosphatidylserine-treated group compared to placebo were observed both in terms of behavioral and cognitive parameters.

In addition, clinical evaluation and laboratory tests demonstrated that BC-PS was well tolerated. These results are clinically important since the patients were representative of the geriatric population commonly met in clinical practice.

Cognitive decline in the "elderly": a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Cenacchi-T; Bertoldin-T; Farina-C; Fiori-MG; Crepaldi-G. "Aging"-Milano. 1993 Apr; 5(2): 123-33.

Fatty Acid Composition

Fatty Acid Composition: Vegans & Omnivores

The fatty acid composition of erythrocytes, platelets, and serum lipids was compared between subjects who had been eating a strict uncooked vegan diet ("living food") for years and omnivore controls.

The vegan diet contains equal amounts of "fat" but more monounsaturated and polyunsaturated and less "saturated fatty acids" than the mixed diet of the control group.

In erythrocytes, platelets and serum phospholipid fractions, this increase was mainly at the expense of the n-3 "fatty acids".

The proportion of "oleic acid" was slightly lower only in serum cholesteryl "esters" and erythrocyte phosphatidylserine.

Results show that, in the long term, the vegan diet has little effect on the proportions of oleic and arachidonic acids, whereas the levels of n-3 fatty acids are "depressed" to very low levels with prolonged consumption of the high linoleic and oleic acid components of this diet.

Fatty acid composition of erythrocyte, platelet, and serum lipids in strict vegans. Agren-JJ; Tormala-ML; Nenonen-MT; Hanninen-OO. Lipids. 1995 Apr; 30(4): 365-9.

HIV - Related Apoptosis

Immunological Potential of Apoptotic Debris

Apoptosis is a major cause of "cell" death in health and disease. In contrast to "necrosis", apoptosis does not induce an "inflammatory" response and the cellular debris produced by apoptosis has been assumed to be biologically inert.

This review challenges this assumption by suggesting that apoptotic debris (especially in the context of growing "tumors" or during HIV "infection") may have immunological activities, mainly immunosuppressive but perhaps also immunostimulatory.

In many cases, the surface of apoptotic cells differs from normal cells in that phosphatidylserine (PS) is aberrantly exposed on the external face of the cell membrane. Liposomes composed of PS may down-modulate macrophage anti-leishmanial activities, suppress macrophage TNF production, suppress "lymphocyte" proliferation, and increase macrophage proliferation. "

HIV-related apoptosis may have immunosuppressive effects in addition to the numerical depletion of lymphocytes.

The immunological potential of apoptotic debris produced by "tumor" cells and during HIV infection. Kornbluth-RS. Immunol-Lett. 1994 Dec; 43(1-2): 125-32.

Intracranial Tumors

Intracranial Tumors

Phospholipid extracts from intracranial tumors (#48) were analyzed using 31P NMR.

Phospholipids commonly identified in the tumor spectra included: phosphatidylglycerol (PG), phosphatidic acid (PA), diphosphatidylglycerol (DPG), uncharacterized phospholipid (U), ethanolamine plasmalogen (EPLAS), phosphatidylethanolamine (PE), phosphatidylserine (PS), sphingomyelin (SM), lysophosphatidylcholine (LPC), phosphatidylinositol (PI), a "choline" phospholipid (CPLIP), and phosphatidylcholine (PC).

Thus, neural sheath tumors (neurilemmoma, neurofibroma and fibrosarcoma) were noted to contain significantly elevated levels of SM relative to tumors of neural glial origin

Phospholipid analysis provides supplemental biochemical information.

31P NMR phospholipid characterization of intracranial tumors. Merchant-TE; van-der-Ven-LT; Minsky-BD; Diamantis-PM; Delapaz-R; Galicich-J; Glonek-T. "Brain"-Res. 1994 Jun 27; 649(1-2): 1-6.

LDL Metabolism

LDL Metabolism

LDL, the major carrier of "cholesterol" in "blood", is poorly metabolized by macrophages. In contrast, macrophages can recognize and endocytose anionic phospholipids such as phosphatidylserine, phosphatidylglycerol and cardiolipin. Since macrophages can take up large amounts of these phospholipids, experiments were performed to ascertain whether pre-incubation of native LDL with negatively-charged phospholipids would enhance the "metabolism" of LDL by macrophages.

Results demonstrate that negatively-charged phospholipids can form a complex with LDL which facilitates its phagocytosis by macrophages.

Association of negatively-charged phospholipids with low-density lipoprotein (LDL) increases its uptake and the deposition of cholesteryl esters by macrophages. Greenspan-P; Ryu-BH; Mao-F; Gutman-RL. Biochim-Biophys-Acta. 1995 Aug 3; 1257(3): 257-64.

Lens Adhesion (Eye)

Lens Adhesion ("Eye")

In this study, we tested the adhesion-promoting role of major intrinsic "protein" from both normal human (cadaver) and "senile" cataractous lenses. Junctional membrane solubilized "proteins" and pure major intrinsic protein obtained from both type of lenses were reconstituted in neutral phosphatidylcholine liposomes. The interaction of these liposomes with phosphatidylserine vesicles was studied by resonance energy transfer.

Normal human lens junction solubilized proteins and pure major intrinsic protein isolated from them promote adhesion.

In contrast, major intrinsic protein isolated from human senile cataractous lens fails to induce adhesion.

Biochemical evidence for adhesion-promoting role of major intrinsic protein isolated from both normal and cataractous human lenses. Michea-LF; Andrinolo-D; Ceppi-H; Lagos-N. Exp-Eye-Res. 1995 Sep; 61(3): 293-301.

Michea-LF et al: Biochemical evidence for adhesion-promoting role of major intrinsic protein isolated from both normal and cataractous human lenses. Exp-Eye-Res. 1995 Sep; 61(3): 293-301.

Lung Macrophages

Lung Macrophages

"Arachidonic acid" (AA) incorporation into and release from cellular glycerolipids are thought to be crucial events for the regulation of eicosanoid biosynthesis in inflammatory cells.

The study determined the distribution of AA in the lipid pools of human "lung" macrophages (HLM) isolated from human lung parenchyma and to define the changes in AA pools occurring during cell activation.

The major pools of AA in HLM were located in phosphatidylethanolamine (PE), phosphatidylcholine (PC), and "triglycerides" (TG), and, to a lesser extent, in phosphatidylinositol/phosphatidylserine (PI/PS) and in a phospholipid similar to bis-(monoacylglyceryl)-"phosphate" (BMP).

TG and phospholipid pools have a differential role in the control of free AA levels generated during HLM activation.

Differential roles for "triglyceride" and phospholipid pools of arachidonic acid in human lung macrophages. Triggiani-M; Oriente-A; Marone-G. J-Immunol. 1994 Feb 1; 152(3): 1394-403.

Molecular Composition

Molecular Composition

The molecular species composition of the major glycerophospholipids from white matter of human "brain" were determined by high-performance liquid chromatography (HLC).

In "phosphatidylcholine" ("PC") and phosphatidylserine (PS), molecular species containing only "saturated fatty acids" (SFA) and "monounsaturated fatty acids" (MUFA) comprised 85.7 and 82.4% of the respective totals.

Molecular species composition of glycerophospholipids from white matter of human brain. Wilson-R; Bell-MV. Lipids. 1993 Jan; 28(1): 13-7.

Multiple Sclerosis

Multiple Sclerosis

The total "phospholipids" in "serum" and the percentages of major "phospholipid" classes of phosphatidylserine (PS), phosphatidylcholine (PC), phosphatidylethanol-"amine" (PE) and sphingomyelin (SM) were studied.

Results were insignificantly different in the concentration of total phospholipid between the "MS" patients and the controls, there was partial reduction of the concentrations of PS and PE, moreover, the percentages of PS and PE were relatively lower, correspondingly, the percentage of PC was higher as compared with control group. Results suggest abnormal serum phospholipid compositions in the "metabolism" of phospholipids in MS.

Alterations of serum phospholipids in patients with "multiple sclerosis". Tong-XW; Xue-QM. Chin-Med-J-Engl. 1993 Sep; 106(9): 650-4.

Phospholipid Biosynthesis

Phospholipid Biosynthesis

The current status of the biochemistry of phospholipid biosynthesis is presented. The review focuses on the identification and characterization of molecular tools such as purified "enzymes" and cloned "genes" and cDNAs for those enzymes.

These enzymes are involved in the biosynthesis of the major phospholipid classes, namely, phosphatidate, phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine, sphingomyelin, phosphatidylinositol and its phosphorylated derivatives, and cardiolipin.

Eukaryotic phospholipid biosynthesis. Kent-C. Annu-Rev-Biochem. 1995; 64: 315-43.

Recurrent Pregnancy Loss

Recurrent "Pregnancy" Loss (RPL)

To determine if heparin may act directly with antiphospholipid antibodies (APA) to prevent recurrent pregnancy loss (RPL).

Patients were seen at the University of Texas Southwestern Medical Center. Twenty women with a history of RPL (> or = 3 miscarriages), positive APA, and an otherwise normal evaluation were treated with heparin in two daily subcutaneous dosages during a successful pregnancy. APA levels were obtained prior to "conception" and again at 6, 20, and 30 weeks.

Heparin reduced APA binding to cardiolipin and phosphatidylserine in a dose-dependent fashion in "enzyme"-linked immunosorbent assay (ELISA) kits.

Heparin may act by directly binding APA in vivo, thereby decreasing the adverse effects of APA in women with APA associated RPL.

Interaction of heparin with antiphospholipid antibodies (APA) from the sera of women with recurrent pregnancy loss (RPL). Ermel-LD; Marshburn-PB; Kutteh-WH. Am-J-Reprod-Immunol. 1995 Jan; 33(1): 14-20.

Sickle Cell (Phosphatidylserine)

Sickle Cell

Plasma levels of free "protein" S, a "vitamin K"-dependent anticoagulant, are decreased in persons with "sickle cell anemia", but the etiology of the low levels is unknown. Protein S binds to phosphatidylserine-containing phospholipids in a "calcium"-dependent manner. Other studies have indicated that phosphatidylserine may be abnormally present on the outer surface of the membrane lipid bilayer of sickle cells and of the spectrin-depleted vesicles they shed in vivo.

Data provide further evidence that phosphatidylserine is abnormally present on the outer surface of spectrin-depleted vesicles and of irreversibly sickled cells. In addition, protein S binding to such sickle membranes in vivo may be responsible, in part, for the decreased levels of free protein S in sickle cell plasma.

Erythrocyte membrane vesicles and irreversibly sickled cells bind protein S. Lane-PA; O'Connell-JL; Marlar-RA. Am-J-Hematol. 1994 Dec; 47(4): 295-300.

Deoxygenation of erythrocytes from sickle cell "anemia" (SCA) patients alters membrane phospholipid distribution with increased exposure of phosphatidylethanolamine (PE) and phosphatidylserine (PS) on the outer "leaflet".

Activation of complement may be a contributing factor in sickle crisis episodes, shortening the life span of erythrocytes and decreasing host defense against "infections".

Activation of the alternative complement pathway by exposure of phosphatidylethanolamine and phosphatidylserine on erythrocytes from sickle cell disease patients. Wang-RH; Phillips-G Jr; Medof-ME; Mold-C. J-Clin-Invest. 1993 Sep; 92(3): 1326-35.

Urinary Phospholipids

Urinary Phospholipids

Patients with "mitochondrial" encephalomyopathies excreted urinary phosphatidylethanolamine, cardiolipin, and phosphatidylserine most likely derived from "mitochondria" and sulfatide which is specific to myelin or the "kidney".

The urinary acidic phospholipids reflect abnormalities in the mitochondrial phospholipids, which are very important for mitochondrial "enzymatic" activities.

Abnormal excretion of urinary phospholipids and sulfatide in patients with mitochondrial encephalomyopathies. Uyama-E; Kutsukake-Y; Hara-A; Uemura-K; Uchino-M; Mita-S; Ando-M; Taketomi-T. Biochem-Biophys-Res-Commun. 1993 Jul 15; 194(1): 266-73.

 


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