Biomedical subjects

B Fuhrman

Publications and source records attributed to B Fuhrman.

At least 37 records · Page 2Linked to original sources

PubMed1996

Macrophage activation with phorbol myristate acetate is associated with cellular lipid peroxidation.

The present study analyzed the association between two major processes that occur during atherogenesis: macrophage activation and peroxidation of the cellular lipids. Macrophage activation was achieved by cell incubation with phorbol myristate acetate (PMA) for 24 h at 37 degrees C, and was determined as: a) PMA concentration-dependent increment in the release of beta-glucuronidase, b) decrement in the procoagulant activity, and c) increment in the release of superoxides from the cells. PMA-induced macrophage activation was accompanied by cellular lipid peroxidation, as measured by increased formation of lipid peroxides (by 435%), thiobarbituric acid-reactive substances (TBARS) (by 26%), and conjugated dienes (by 77%) in comparison with control nonactivated cells. The maximal effect of PMA on lipid peroxidation in macrophages was achieved within 1 h of cell incubation with PMA. This effect was demonstrated in J-774 A.1 macrophages, as well as in mouse peritoneal, macrophages, U-937 and P-338 macrophage cell lines. Upon incubation of macrophages with 4 alpha phorbol 12, 13 didecanoate, an analogue of PMA (which, unlike PMA, does not activate protein kinase C), macrophage lipid peroxidation was lower compared with PMA, suggesting a role for protein kinase C in cellular lipid peroxidation. Analysis of cellular antioxidants under PMA-induced macrophage activation revealed a decrease of 50% in total glutathione, and in catalase levels following treatment with 100 nM PMA compared with control cells. In summary, our study demonstrates that PMA-activated macrophages undergo significant lipid peroxidation, which is associated with reduced activity of the cellular antioxidative system.

Animals↗

PubMed1995

Consumption of red wine with meals reduces the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation.

The effect of consumption of red or white wine (11% alcohol) with meals on the propensity of plasma and low-density lipoprotein (LDL) to undergo lipid peroxidation was studied in 17 healthy men who were divided into two groups: 8 received 400 mL red wine/d for 2 wk, and 9 received a similar amount of white wine. Red wine consumption for 2 wk resulted in a 20% reduction in the propensity of plasma to undergo lipid peroxidation (in the presence of a free-radical-generating system) as determined by the thiobarbituric acid reactive substances (TBARS) assay. In parallel, red wine consumption reduced the propensity of the volunteers' LDL to undergo lipid peroxidation (in response to copper ions) as determined by a 46%, 72%, and 54% decrease in the content of TBARS, lipid peroxides, and conjugated dienes in LDL, respectively, as well as by a substantial prolongation of the lag phase required for the initiation of LDL oxidation. On the contrary, dietary consumption of white wine for 2 wk resulted in a 34% increase in plasma's propensity to undergo lipid peroxidation and also in a 41% increased propensity of the LDL to undergo lipid peroxidation. The antioxidant effect of dietary red wine on plasma lipid peroxidation was not secondary to changes in the plasma vitamin E or beta-carotene content but could be related to the elevation of polyphenol concentration in plasma and LDL. Thus, some phenolic substances that exist in red wine, but not in white wine, are absorbed, bind to plasma LDL, and may be responsible for the antioxidant properties of red wine.

Adult↗

PubMed1995

Low density lipoprotein-cholesteryl ester-derived linoleic acid is mainly incorporated into the phospholipid component of the macrophages.

The cellular metabolism of the cholesterol in the low density lipoprotein cholesteryl ester (LDL-CE) moiety is well characterized, whereas the cellular fate of the fatty acid (mainly linoleic acid) in the LDL-CE has not been studied in detail. The distribution of the LDL-CE-derived linoleic acid among cellular lipids was studied in J-774 A.1 macrophages, using LDL that was radiolabeled in the linoleic acid of its CE moiety. Macrophages were incubated with radiolabeled LDL for 4 h at 4 degrees C, washed and further incubated for up to 24 h at 37 degrees C in a fresh medium (without LDL). The distribution of the linoleic acid among cellular lipids was then analyzed. After 20 min of incubation, most of the linoleic acid was found in the CE fraction as a constituent of the internalized LDL, and the CE-associated linoleate was progressively decreased. In parallel, the linoleic acid was found to be esterified into the macrophage phospholipids (mostly in the macrophage phosphatidyl choline fraction), accounting for up to 62% of the total cellular labeled linoleic acid after 24 h of incubation. We conclude that the fatty acid derived from the hydrolysis of the LDL-CE moiety in macrophages is mainly incorporated into the cellular phospholipids where it can serve for various cellular metabolic processes.

Animals↗

PubMed1994

[Plasma lipid peroxidation: inhibited by drinking red wine but stimulated by white wine].

The effects of drinking red or white wine (11% alcohol) on the propensity of plasma and low density lipoprotein (LDL) to undergo lipid peroxidation (LP) was studied. 8 healthy men drank 400 ml of red wine a day for 2 weeks and 9 drank white wine similarly. The red wine supplementation resulted in a 20% similarly. The red wine supplementation resulted in a 20% reduction in the propensity of their plasma to undergo LP (in the presence of a free radical-generating system) and a 46% reduction in that of their LDL to undergo LP (in response to copper ions). Contrarily, drinking white wine for 2 weeks resulted in a 33% increase in propensity of plasma to undergo LP and in a 57% increase in that of LDL to undergo LP. The antioxidant effect of drinking red wine on plasma LP can be related to increase in plasma high density lipoprotein concentration, as well as to increase in plasma and LDL polyphenols. We conclude that some phenolic substance present in red, but not in white wine, may be responsible for the antioxidative properties of red wine supplementation for LDL LP, and thus may possess antiatherogenic properties.

Alcohol Drinking↗

PubMed1994

Iron induces lipid peroxidation in cultured macrophages, increases their ability to oxidatively modify LDL, and affects their secretory properties.

The present study demonstrates for the first time that iron ions can induce lipid peroxidation in intact macrophages without causing cell death. Macrophage lipid peroxidation increases cell-mediated oxidation of LDL, enhances the release of interleukin 1 and inhibits the release of apolipoprotein E from the macrophages. When cultured macrophages were exposed to ferrous ions (50 microM FeSO4) for 4 h at 37 degrees C, cellular lipid peroxidation (measured by analyses of malondialdehyde (MDA), conjugated dienes (CD), and lipid peroxides (PD)) increased 2-4-fold in comparison with non-treated cells. This process was iron-dose dependent, reached its maximum after 4 h of incubation, and was accompanied by 68% and 53% reductions in the content of the cellular linoleic (18:2), and arachidonic acid (20:4), respectively, and by 29% and 36% reductions of cellular vitamin E and vitamin A, respectively. Cell viability (measured by trypan blue exclusion, by [3H]thymidine incorporation into DNA, by analysis of the release of lactate dehydrogenase (LDH) or [3H]adenine), and cell morphology (studied by scanning electron microscopy) were not significantly affected by the iron-induced oxidative stress. Manitol and dimethylthiourea (DMTU), but not catalase or superoxide dismutase (SOD), significantly inhibited iron-induced cellular lipid peroxide formation, suggesting that hydroxyl radical, but not superoxides or hydrogen peroxides, mediated the iron-induced cellular lipid peroxidation. Incubation of LDL (0.2 mg of protein/ml) with oxidized macrophages resulted in LDL lipids peroxidation, as evidenced by an 8-fold increase in the LDL associated MDA in comparison with LDL that was incubated under similar conditions with non-oxidized macrophages. Furthermore, oxidation of LDL by oxidized macrophages in the presence of copper ions (10 microM CuSO4) was 2-fold higher in comparison with oxidation of LDL by non-oxidized macrophages. The release of apolipoprotein E from oxidized macrophages decreased by 50%, whereas macrophage release of beta-glucuronidase and of interleukin-1 beta increased by 83% and by a factor of 6, respectively. This study demonstrates for the first time that iron ions induce oxidation of the cellular polyunsaturated fatty acids in intact macrophages and that this cellular lipid peroxidation can subsequently induce LDL oxidation.

Animals↗

PubMed1994

Effect of dietary supplementation of red or white wine on human blood chemistry, hematology and coagulation: favorable effect of red wine on plasma high-density lipoprotein.

Twenty healthy males were divided into two groups: 10 subjects were supplemented for 2 weeks with 400 ml of red wine (11% alcohol) per day and the other 10 subjects were given 400 ml of white wine (11% alcohol) per day for a similar period. Blood samples were drawn prior to wine supplementation, after 1 week and at the end of the study. No significant effects were found on plasma concentrations of urea, creatinine, bilirubin, creatine kinase, amylase, blood cell counts, platelet counts and platelet aggregation. Both red- and white-wine supplementation resulted in a transient minor reduction in plasma glucose concentration and in a minor elevation in blood coagulation properties such as prothrombin time and partial thromboplastin time. Red (but not white) wine resulted in an 11 and 26% increment in plasma triglyceride concentrations after 1 and 2 weeks of supplementation, respectively. Plasma cholesterol, as well as very-low- and low-density-lipoprotein levels did not change during the 2 weeks of red- or white-wine supplementation. The most impressive effect of red-wine intake was a significant (p < 0.01) increase in plasma high-density lipoprotein (HDL) cholesterol and in plasma apolipoprotein A-I concentrations by up to 26 and 12%, respectively. These effects were not observed after the intake of white wine. We conclude that the major effect of red-wine supplementation (about 40 g of alcohol per day for a period of 2 weeks) was a significant increase in plasma HDL concentration which may contribute to the reduced risk for cardiovascular diseases observed in red-wine drinkers.

Adult↗

PubMed1992

Proteins derived from platelet alpha granules modulate the uptake of oxidized low density lipoprotein by macrophages.

Activated platelets secrete from their alpha granules a protein-like factor which stimulates the uptake of oxidized low-density lipoprotein (Ox-LDL) by macrophages. The aim of the present study was to evaluate the effect of three purified proteins obtained from platelet alpha granules: platelet-derived growth factor (PDGF), platelet factor-4 (PF-4), and beta-thromboglobulin (B-TG), on the uptake of Ox-LDL by macrophages. Cellular degradation of Ox-LDL by the J-774 A.1 macrophage-like cell line, that was preincubated for 18 h at 37 degrees C, with increasing concentrations of partially purified PDGF, (designated PDGF-CMS-III) was increased by up to 36% in comparison to control cells preincubated without PDGF. This effect was due to PDGF-mediated increase in the number of macrophage receptors for Ox-LDL. The enhanced uptake of Ox-LDL by PDGF resulted in an increase in cellular cholesterol content. Preincubation of macrophages with two types of recombinant PDGF dimers (10 ng/ml), revealed that PDGF-BB stimulated Ox-LDL cellular degradation by 64%, whereas PDGF-AB demonstrated only 34% stimulation, in comparison to control cells that were not treated with PDGF. The stimulatory effect of PDGF-CMS-III and PDGF-AB were reduced by 20% and 28%, respectively, when incubated in the presence of H-7, a specific protein kinase C inhibitor. When macrophages were preincubated with B-TG, cellular uptake of Ox-LDL was reduced by up to 30% at 100 ng B-TG/ml. This effect, however, was obtained only when B-TG was present in the incubation medium. Cellular degradation of Ox-LDL was not affected by preincubation of the cells with PF-4. Pretreatment of PCM with anti-PDGF or anti-B-TG antibodies abolished the effects of PCM on Ox-LDL degradation by macrophages. PDGF, thus, may represent the protein-like factor present in PCM which stimulates Ox-LDL degradation by macrophages, whereas B-TG may have a role in the recognition of PCM particles by the macrophage scavenger receptor. Modulation of macrophage cholesterol content by proteins secreted from activated platelets may have an important role in foam cell formation and atherosclerosis.

Antibodies↗

PubMed1992

Involvement of the macrophage low density lipoprotein receptor-binding domains in the uptake of oxidized low density lipoprotein.

Macrophages, unlike most other cells, possess both low density lipoprotein (LDL) and scavenger receptors. The scavenger receptor has been shown to mediate the uptake of oxidized LDL (ox-LDL), which ultimately leads to cholesterol loading of the macrophages. The present study was undertaken to define epitopes on ox-LDL that are important for lipoprotein binding to macrophages and to ascertain whether ox-LDL can bind to the LDL receptor. Monoclonal antibodies (Mabs) directed against several epitopes along the apolipoprotein B-100 (apo B-100) molecule were used. LDL (300 micrograms/ml) was oxidized by incubation with 10 microM CuSO4 for 24 hours. Ox-LDL, as opposed to acetylated LDL (ac-LDL), reacted with Mabs directed against the LDL receptor-binding domains (Mabs B1B6 and B1B3). Similarly, uptake of ox-LDL but not ac-LDL by a murine J774 macrophage-like cell line was inhibited by as much as 40% after using Mab B1B6. The anti-LDL receptor antibody IgG-C7 also inhibited 125I-ox-LDL uptake by macrophages by 60%. Chromatography on heparin-Sepharose columns of LDL that was partially oxidized for only 3 hours resulted in two fractions: an unbound fraction with characteristics similar to those of ox-LDL and a bound fraction similar to native LDL. Macrophage degradation of the unbound fraction was inhibited by Mab IgG-C7 and Mab B1B6, which are directed toward the LDL receptor and the LDL receptor-binding domains on apo B-100, respectively. When incubated with three types of macrophages, J774 macrophage cells, mouse peritoneal macrophages, and human monocyte-derived macrophages, excess amounts of unlabeled ox-LDL, like native LDL but unlike ac-LDL, substantially suppressed the uptake and degradation of 125I-labeled LDL. Similar studies with fibroblasts, however, revealed that unlabeled LDL but not unlabeled ox-LDL or ac-LDL competed with 125I-LDL for cellular uptake and degradation. Mab directed against epitopes on the amino terminus domain of apo B-100 (C14) demonstrates a similar immunoreactivity with ox-LDL and native LDL but a much lower reactivity with ac-LDL. Mab C14 inhibited macrophage degradation of ox-LDL by 34% but had no inhibitory effect on the uptake of native LDL or ac-LDL. Thus, the ac-LDL and LDL receptor-binding domains as well as a unique epitope on the amino terminus of apo B-100 may be involved in macrophage binding of ox-LDL.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Serotonin increases macrophage uptake of oxidized low density lipoprotein.

Macrophage uptake of oxidized low density lipoprotein leads to cellular cholesterol accumulation and foam cell formation. Atherogenesis involves platelet activation with subsequent serotonin release. Incubation of J-774 A.1 murine macrophages as well as mouse peritoneal macrophages with serotonin for 2-18 hours at 37 degrees C, followed by cell wash and a further incubation of the cells for 18 hours in the presence of oxidized LDL (protein concentration 10-75 mg/l), resulted in up to 85% elevation in cellular uptake of the lipoprotein. Maximal effect was found after preincubation of the cells for 18 hours in the presence of 25 mumols/l serotonin. At lower or higher serotonin concentrations and with longer or shorter times of preincubation, cellular degradation of oxidized LDL was reduced. Under similar incubation conditions (with oxidized LDL), macrophage cholesterol accumulation was also increased by serotonin from 65 to 75 micrograms cholesterol per mg cell protein. This effect of serotonin was the result of a serotonin-mediated increase in the affinity of oxidized LDL towards its receptor without a significant change in the number of the receptors. Specific binding of serotonin to J-774 A.1 macrophages was demonstrated. Ten mumols/l of ketanserine (serotonin antagonist) completely blocked the stimulatory effect of serotonin on the cellular uptake of oxidized LDL. After injection of serotonin into the peritoneal cavity of thioglycolate-stimulated mice (250 nmol/mouse), the collected macrophages showed a 34% enhanced degradation of oxidized [125I]LDL compared with control cells collected from mice that were not injected with serotonin. Platelets from patients with carcinoid syndrome contained about twice as much serotonin as platelets from healthy subjects. Platelets were activated with collagen (1 mg/l) and platelet-conditioned medium was collected. Platelet-conditioned medium from healthy subjects enhanced the cellular uptake of oxidized LDL by 33%, whereas a similar concentration (protein concentration 15 mg/l) of platelet-conditioned medium from the patients increased macrophage uptake of oxidized LDL by 75%. Incubation of macrophages with platelet conditioned medium in the presence of ketanserine completely abolished the stimulation of oxidized LDL degradation, implying serotonin involvement in this process. We conclude that serotonin enhancement of oxidized LDL uptake by macrophages may be relevant in atherogenesis where both platelet activation and foam cell formation occur.

Animals↗

PubMed1991

Lipid-protein particles secreted from activated platelets reduce macrophage uptake of low density lipoprotein.

Cellular uptake of low density lipoprotein (LDL) was reduced by 30-40% in macrophages that were preincubated with platelet conditioned medium (PCM) obtained from activated platelets. LDL mediated cholesterol accumulation and cholesterol esterification in macrophages were substantially inhibited by macrophages preincubation with PCM. This inhibitory effect was found to be dose dependent, and resulted from a reduction in the number of LDL receptors (decrement of 35% in "apparent Vmax"). The active component in PCM was present only in medium obtained from activated platelets and was found to be of a molecular weight higher than 25,000 dalton. It comprised of both protein and cholesterol but upon PCM delipidation only the lipid fraction demonstrated the inhibitory effect on macrophage uptake of LDL. Specific uptake of the PCM lipoprotein-like particle via the scavenger receptor on macrophages was found to be essential for the expression of LDL receptor reduced activity. Furthermore, LDL mediated cholesterol esterification was not inhibited by PCM in U937 macrophages, a cell line that lacks the scavenger receptors. It is concluded that activated platelets secrete a lipoprotein-like particle which is recognized by the macrophage scavenger receptor. Subsequent to PCM-macrophage interaction, cellular LDL uptake was reduced. This effect could be attributed to the PCM lipid constituents.

Blood Platelets↗

PubMed1991

Activated platelets secrete a protein-like factor that stimulates oxidized-LDL receptor activity in macrophages.

Platelet secretory products were shown to modulate the interaction between lipoproteins and their receptors on macrophages. Preincubation of macrophages for 2 h at 37 degrees C with platelet conditioned medium (PCM), followed by its removal and a further 5-h incubation in the presence of oxidized-LDL (Ox-LDL), resulted in increased cellular degradation of Ox-LDL (34%), stimulation of cellular cholesterol esterification (31%), and mass accumulation of esterified and nonesterified cholesterol (25% and 41%, respectively). These effects were found to be the result of a PCM-mediated increase in the number of Ox-LDL receptors on macrophages. PCM was shown to interact with the macrophage scavenger receptor. Enhanced Ox-LDL uptake by macrophages preincubated with PCM could not be reproduced when PCM remained in the incubation medium. Maintenance of PCM in the incubation medium reduced Ox-LDL uptake by macrophages (40%) and was shown to be PCM dose-dependent. Whereas incubation at 37 degrees C demonstrated enhanced uptake of Ox-LDL, preincubation of macrophages with PCM at 4 degrees C exhibited a 64% reduction in Ox-LDL-mediated cellular cholesterol esterification. Thus, PCM internalization by macrophages after its binding to the scavenger receptor is required to promote the enhancing effect of PCM on Ox-LDL uptake by macrophages. PCM activity was associated with platelet degranulation, and was recovered in the protein fraction of PCM. It was found to be heat- and trypsin-labile with a molecular weight greater than 25,000. PCM obtained from platelets derived from a patient with alpha granules deficiency failed to enhance the uptake of Ox-LDL by macrophages, suggesting that the active protein-like factor in PCM originated from platelet alpha granules. These results indicate that a platelet-secreted protein-like factor can modulate macrophage uptake of Ox-LDL with subsequent effect on foam cell formation.

Animals↗

PubMed1990

Intralipid infusion in patients with familial hypercholesterolemia. Effect of serum and plasma lipoproteins on platelet aggregation and on macrophage cholesterol metabolism.

Intralipid infusion into normal volunteers was recently shown to possess anti-atherogenic properties. We studied the effect of intralipid infusion in patients with severe Familial Hypercholesterolemia (FH) refractory to conventional therapy. FH patients and normal subjects, who served as controls, were given an intravenous infusion of intralipid for 6 h. Serum samples taken from both groups before, during and after intralipid infusion were studied for their ability to inhibit cellular cholesterol accumulation by macrophages. A significantly lower rate of cellular cholesterol esterification (of 46%, P less than 0.005 and 44%, P less than 0.005 in patients and normals, respectively) was demonstrated in macrophages incubated with serum obtained during intralipid infusion compared to those incubated with preinfusion serum. The maximal effect was demonstrated with serum samples taken at the end of the infusion, but the inhibitory effect persisted even at 24 h post-infusion. It was found that chylomicron like particles could induce the above-mentioned effects on macrophage cholesterol esterification. A significant decrement of 50% (P less than 0.005) in aggregation of platelets isolated from plasma samples taken during and after intralipid infusion from both groups was demonstrated, when compared to platelets isolated in the preinfusion state. This effect persisted 18 h subsequent to infusion. We conclude that intralipid infusion abolishes serum ability to stimulate cholesterol esterification in cultured macrophages, and exhibits inhibitory effects upon platelet aggregation. If similar events occur in the arterial wall, intralipid might inhibit foam cell formation.

Adolescent↗

PubMed1989

Modification of LDL by platelet secretory products induces enhanced uptake and cholesterol accumulation in macrophages.

LDL modified by incubation with platelet secretory products caused cholesterol accumulation and stimulation of cholesterol esterification in mouse peritoneal macrophages. Its uptake by the macrophages was a receptor-mediated process, not susceptible to competition by acetyl-LDL or polyanions suggesting independence of the scavenger receptor. Stimulation of the esterification process in macrophages by this modified LDL was inhibited by the lysosomal inhibitor chloroquine, indicating requirement for cellular uptake and lysosomal hydrolysis of the lipoprotein. Within the cell, the modified LDL inhibited cellular biosynthesis of triglycerides in a manner similar to the action of acetyl-LDL but different to the effect of native LDL. In the presence of HDL, acting in the medium as an acceptor for cholesterol, a low rate of cholesterol efflux from cells incubated with this modified LDL as well as with acetyl-LDL was demonstrated. A small reduction in cholesteryl ester synthesis was found in these cells, compared to a 60% reduction in cells incubated with native LDL. Thus it was demonstrated that LDL modified by platelet secretory products could induce macrophage cholesterol accumulation even though it was recognized and taken up via the regulatory LDL receptor.

Adult↗

PubMed1989

New pigtail catheter for pleural drainage in pediatric patients.

The conventional method of pleural drainage is tube thoracotomy, accomplished by chest wall dissection and blunt puncture. While this method is successful, it is relatively traumatic. We have designed a pigtail catheter which may be inserted into the pleural space by a modified Seldinger technique. This 8.5-Fr polyurethane catheter has six side ports inside its circular distal end. An airtight plastic bag is attached to the insertion needle to confirm pleural placement. Nineteen catheters were inserted in 16 neonates and small children with either pneumothorax or pneumomediastinum. No complications were noted. All but one pneumothorax was successfully evacuated; however, the pneumomediastinum reaccumulated. Insertion proved to be safe, simple, and atraumatic. This pigtail pleural drainage catheter provides an alternative to standard tube thoracotomy.

Catheterization↗

PubMed1989

Platelet-modified low density lipoprotein induces macrophage cholesterol accumulation and platelet activation.

Low density lipoprotein (LDL), modified by chemical or biological means, was shown to induce macrophage cholesterol accumulation. The cholesterol and protein contents of LDL were decreased (by 10 and 15%, respectively) by incubation of the LDL for 2 h at 37 degrees C with normal washed platelet suspension or with platelet-conditioned medium; these decreases were not affected by platelet activation. The platelet-modified LDL caused a greater increase (by up to 15%) in collagen-induced, in vitro platelet aggregation than control LDL. Incubation of mouse peritoneal macrophages with platelet-modified LDL for 18 h at 37 degrees C resulted in an elevation of the macrophage cholesterol ester content (by 35-50%) as well as an increase in the cholesterol esterification rate (by 40-70%), compared with the effect of control LDL. Macrophage cholesterol synthesis, however, was significantly decreased (by 40-50%), compared with the effect of control LDL. The effect of LDL treated by platelet-conditioned medium was similar to that of platelet-modified LDL. The effect of platelet-modified LDL on macrophage cholesterol esterification was maximal within 24 h of incubation, and it was not significantly affected by inhibition of cholesterol synthesis. The platelet-modified LDL was taken up by the macrophages in a saturable fashion and its uptake was competitively inhibited by LDL, but not by acetylated LDL. We conclude that platelet-modified LDL interacts with the LDL receptor and induces macrophage cholesterol accumulation. Since the modified lipoprotein induces in vitro foam cell formation and platelet activation, platelet-modified LDL could be considered to be pro-atherogenic.

Animals↗

PubMed1989

[Intralipid infusion in familial hypercholesterolemia].

Intralipid, used for intravenous alimentation and containing triglyceride emulsion particles and phospholipid liposomes, has been shown to induce regression of atherosclerosis in experimental animals. Intravenous infusions of Intralipid were given to 2 patients with severe familial hypercholesterolemia refractory to conventional therapy, and to control subjects. Intracellular cholesterol esterification was inhibited in macrophages incubated with serum taken during infusions as compared to the preinfusion state, with maximal effect after 6 h of infusion. A significant decrease in platelet aggregation was also demonstrated in both groups, which persisted for 18 h after infusion. We conclude that infusion of Intralipid may have anti-atherogenic effects and plan to use it in patients with severe atherosclerosis.

Cholesterol↗

PubMed1989

[Platelet-modified LDL: uptake and metabolism in macrophages].

Mouse peritoneal macrophages accumulate large amounts of cholesterol ester when incubated with chemically or biologically modified lipoproteins. Incubation of LDL with platelet secretory products for 2 hours at 37 degrees C decreases its protein and cholesterol content. Subsequently this modified LDL, named PCM-LDL, enhances in-vitro platelet aggregation. When it is incubated with cultures of macrophages, cholesterol accumulates in the cells and esterification is increased. PCM-LDL is taken up by macrophages via a receptor-mediated mechanism, independent of the scavenger receptor for acetyl-LDL. Its degradation in lysosomes is required for stimulation of cholesterol ester synthesis.

Animals↗

PubMed1988

Extracorporeal membrane oxygenation in children. New trends.

At the Children's Hospital of Pittsburgh the extracorporeal membrane oxygenation program was started in 1980. The results of our experience from 1980 to 1985 were previously reported. In the past 2 years 39 additional newborn infants have been treated with this modality, with an overall survival rate of 79% (31/39). This survival rate is much better than that obtained in 33 neonates who had been treated in the previous 5 years (54%; p less than 0.05). A new aspect of our extracorporeal membrane oxygenation program is the use of total apneic lung rest for persisting pulmonary interstitial emphysema during support with the oxygenator. Six neonates were treated with this technique because of worsening pulmonary interstitial emphysema during extracorporeal circulation. Five of them survived. Another indication for extracorporeal membrane oxygenation in our pediatric population has been left ventricular or biventricular failure after cardiopulmonary bypass. Four of our seven patients treated for this indication are long-term survivors. At present, because of the impossibility of using other forms of left ventricular assist devices in the pediatric population, it seems that extracorporeal membrane oxygenation is the most effective treatment for left ventricular failure after cardiopulmonary bypass. From our experience, even in the absence of long-term follow-up of patients supported with extracorporeal membrane oxygenation, it appears that the benefits of this therapeutic modality far exceed the risks in the high-risk population for which it is being used.

Cardiopulmonary Bypass↗