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Biomedical subjects

M Naruszewicz

Publications and source records attributed to M Naruszewicz.

At least 37 records · Page 2Linked to original sources
PubMed1999

Increased levels of factor VII, fibrinogen and activity of plasminogen activator inhibitor during postprandial triglyceridemia in patients with ischemic heart disease confirmed by angiography.

BACKGROUND AND AIM: Impaired elimination of triglycerides (TG) after postprandial lipemia is often observed in patients with ischemic heart disease (IHD). Longer retention of TG-rich lipoproteins in the circulation may in turn be the cause of hemostatic disturbances in the form of hypercoagulation. The aim of this study was to evaluate the influence of postprandial lipemia on the hemostatic system in normolipemic patients with angiographically documented atherosclerotic changes of coronary arteries. METHODS AND RESULTS: 20 males under 60 years of age with IHD and 10 healthy males matched for age were studied. Hemostatic and lipid parameters were determined in blood collected before (fasting) and after (2, 4, 6 and 8 hours) an oral fat load (200 ml of 30% cream). A statistically significant increase in factor VII (FVIIc-%) was found during postprandial lipemia in comparison with fasting. Although in patients with IHD the area under the curve for FVIIc was not significantly different than in the control group, it was observed that FVIIc in the IHD group exceeded the fasting level earlier (4, 6 and 8 h) than in controls (8 h). Levels of FVIIc reached for the IHD group: fasting value = 96.3 +/- 16.3; postprandial 4 h = 103.2 +/- 21.3, 6 h = 105.2 +/- 21.8, 8 h = 106.0 +/- 21.4; for the controls: fasting value = 96.8 +/- 17.2; postprandial 8 h = 107.7 +/- 22.0. In the IHD group, unlike in controls, postprandial lipemia was accompanied by a statistically significant rise in fibrinogen levels (Fb-g/l) as compared with fasting (fasting value = 3.69 +/- 0.59; postprandial 2 h = 3.89 +/- 0.65, 4 h = 3.93 +/- 0.63). Mean values for PAI-1 were lower in the IHD than in the control group, but PAI-1 activity during postprandial lipemia rose earlier in the IHD group (4 and 6 h) than in the controls (6 h). PAI-1 levels were in the IHD: fasting values = 1.4 +/- 1.2; postprandial 4 h = 2.3 +/- 1.6, 6 h = 2.5 +/- 1.7; in the control: fasting value 2.9 +/- 1.7; postprandial 6 h = 3.9 +/- 2.0. The level of fragment 1 + 2 (F1 + 2) during postprandial lipemia decreased in both groups. CONCLUSIONS: The lipemic stimulus in fasting normolipemics induces a hypercoagulant effect with greater changes in patients with ischemic heart disease than in healthy subjects. Longer periods of postprandial lipemia might constitute an additional factor promoting thrombus formation in patients with dysfunction of the vascular endothelium.

Adult↗
PubMed1998

LDL-R and Apo-B-100 gene mutations in Polish familial hypercholesterolemias.

A group of 30 Polish families with clinical signs of familial hypercholesterolemia was studied for the presence of germ-line mutations in the LDL-R and ApoB-100 genes. Screening of the LDL-R gene was performed at the genomic DNA level by single-strand conformation polymorphism analysis of all 18 exons and extended by sequencing of polymerase chain reaction (PCR) products showing abnormalities. The occurrence of large LDL-R gene alterations was evaluated by analysis of restriction enzyme patterns on Southern blots and using the long-PCR technique. The ApoB-100 gene was studied by combined allele-specific and asymmetric PCR for the occurrence of the common B-3500 missense mutation G to A at nucleotide position 10,708. Germ-line mutations were found in 17 families. In 12 of them LDL-R gene mutations were detected. Three of 11 different mutations had previously been described in other populations (3-bp deletion of codon 197; Ser156Leu; Gly571Glu). Of the mutations not previously recognized and identified in Polish families, there were three small deletions (2-bp deletion AG at codon 291; 4-bp deletion CCCT at codons 661-662; 1-bp deletion A at codon 830), and four point mutations (Arg239Stop, Cys331Stop, Asn543Ser, Gln665Stop). Additionally, one large (approximately 1-kb) LDL-R gene deletion between exons 6 and 9 was identified. In five families, the B-3500 mutation within the ApoB-100 gene was revealed.

Apolipoproteins B↗
PubMed1998

Leptin receptor isoforms expressed in human adipose tissue.

Leptin and its structural gene, Ob, are exclusively expressed in adipose tissue. Leptin is secreted into the blood and is responsible for fat mass regulation via leptin receptors in the hypothalamus. This has been considered the major role of leptin, but leptin receptor isoforms are expressed not only in the brain but also in most other tissues in humans and rodents: heart, placenta, lung, liver, muscle, kidney, pancreas, spleen, thymus, prostate, testes, ovary, small intestine, and colon. This implicates leptin regulation in other systems apart from fat mass regulation, and leptin action has been demonstrated in human fetal development and reproductive development, liver metabolism, hematopoiesis, and insulin secretion. Four splice variants of the leptin receptor have been identified in humans: the long isoform huOb-R and the shorter isoforms B219.1 to B219.3. It is known that the long isoform has full intracellular signaling capacity, and is responsible for anorectic action in the hypothalamus. The roles of the other isoforms are yet to be elucidated. Here, we report the identification by reverse transcriptase-polymerase chain reaction (RT-PCR) of three leptin receptor isoforms coexpressed in human visceral adipose tissue: the long isoform huOb-R and the short isoforms huB219.1 and huB219.3. The possible roles of these isoforms are discussed.

Adipose Tissue↗
PubMed1996

[Evaluation of lipoprotein (a) and fibrinogen levels in men after premature myocardial infarction and in their sons].

Lipoprotein (a) and fibrinogen admittedly are independent risk factors of coronary heart disease. Since Lp (a) has been shown to inhibit plasminogen binding to endothelial cells and to fibrin monomers, this led to the speculation that high Lp (a) levels in plasma could interfere with fibrinolysis. Therefore the aim of our work was to estimate the lipoprotein (a) and fibrinogen levels and to find correlation between lipoprotein (a) and fibrinogen levels at the men after a myocardial infarction and also at their sons. We examined 33 men of age 31-57 after a myocardial infarction and their 18 sons 4-14 years old. The control group consisted of 40 men of age 18-57 and their 19 sons 5-14 years old. The Lp (a) was determined with electroimmunodiffusion method and fibrinogen by Clauss method. The fibrinogen level in the examined group was found to be statistically significantly higher (338 mg/dl) than in the control group (313 mg/dl). There was no correlation between Lp(a) and fibrinogen concentration. In the group of sons of patients mean fibrinogen and Lp (a) levels were similar to those of the control group. However there was a negative correlation between the fibrinogen and the triglycerides concentration in sons of patients but not in the control group. The results seem to confirm the significance of fibrinogen as a risk factor for the development of the coronary heart disease.

Adolescent↗
PubMed1996

[Effect of dietetic recommendations on the level of some lipid and hemostatic parameters in offspring of parents with risk factors for coronary heart disease].

Atherosclerosis, the precursor of coronary heart disease may originate in childhood. The atherogenic potential of food is related to its cholesterol and saturated-fat content. The study population consisted of children from CHD-parents under the age 12 years with plasma total cholesterol > 170 mg/dl, LDL-Ch > 90 mg/dl and ApoB > 70 mg/dl. All the patients were advised a 6 month diet following National Program of Cholesterol Prevention recommendation. Plasma, TCh, LDL-Ch, ApoB, TG, Ch-esters saturated/unsaturated ratio and platelet factor 4 concentration decreased, LCAT activity and Ch-esters unsaturated increased during study period. We observed interesting correlation between: PF4 and ApoB, PF4 and LDL-Ch and PF4 and HDL-ECh 18:3. Our data show, that proper diet can modify risk factors of CHD in children with family history of CHD.

Apolipoproteins B↗
PubMed1993

Simvastatin inhibits the oxidation of low-density lipoproteins by activated human monocyte-derived macrophages.

Human monocyte-derived macrophages treated with increasing concentrations of the HMG-CoA reductase inhibitor, simvastatin, showed a dose-dependent decrease in superoxide formation in response to activation by phorbol myristate acetate. As a consequence, they oxidized LDL much less than untreated cells. Addition of exogenous mevalonic acid to simvastatin-treated macrophages restored their ability for superoxide production and for oxidative modification of LDL. These results indicate that simvastatin might prevent atherosclerosis by additional mechanisms besides its hypocholesterolemic activity.

Drug Interactions↗
PubMed1993

Influence of probucol on enhanced LDL oxidation after fish oil treatment of hypertriglyceridemic patients.

The susceptibility of low-density lipoprotein (LDL) to oxidation was studied in hypertriglyceridemic men (5 with type III and 5 with type IV) at baseline on a low-saturated-fat, low-cholesterol diet, after 6 weeks of dietary supplementation with fish oil (Promega, 12 g/d), and after 6 weeks of fish oil combined with probucol (500 mg BID). The relative content of n-3 polyunsaturated fatty acids in plasma and LDL was increased during the two treatment periods, and a low alpha-tocopherol to n-3 polyunsaturated fatty acids ratio was observed. Plasma thiobarbituric acid-reactive substances (TBARS) levels were unchanged after 6 weeks of fish oil, but the ratio of lipid peroxides to the reduced triglyceride (TG) levels (MDA:TG) was significantly higher (P < .01). Addition of probucol lowered both absolute levels of TBARS (P < .01) and the MDA to TG ratio (P < .001). The susceptibility of LDL to Cu(2+)-catalyzed oxidation was evaluated over a 5-hour time course by determining TBARS formation, free amino group levels, and changes in LDL electrophoretic mobility. TBARS levels that were higher in native LDL (1.019 < d < 1.050 g/mL) after 6 weeks of fish oil than at baseline (P < .01) were reduced 52.3 +/- 11.3% by the addition of probucol (P < .001). With fish oil alone, TBARS production after exposure of LDL to Cu2+ for 5 hours was increased 17.0 +/- 5.8% compared with corresponding baseline values (P < .001), whereas a 64.1 +/- 14.3% reduction from the previous period was observed with fish oil + probucol (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Oxidative modification of lipoprotein(a) and the effect of beta-carotene.

Lipoprotein (a) [Lp(a)] particles isolated and purified from human plasma were found to be oxidatively modified when incubated in vitro with human mononuclear cells or Cu2+. This modification, which involved lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS), caused marked changes in the structure and biological properties of Lp(a). Relative to native Lp(a), oxidized particles showed decreases of free amino groups, protein fragmentation, increased negative charge, and high aggregation ability. They were taken up and degraded readily by macrophages in vitro, inducing cholesteryl ester accumulation. When apolipoprotein (a) [apo(a)] was clipped off by exposure to dithiothreitol (DTT), the remaining particle was degraded by macrophages at a significantly lower rate. This observation implies that oxidative modification of apo(a) may have an influence on Lp(a) recognition by scavenger receptors of macrophages. Under the same experimental conditions, low-density lipoprotein (LDL) concentrations equal to those of Lp(a) showed a lower susceptibility to oxidation. This was probably due to higher vitamin E (30% more) and beta-carotene (40% more) content compared with Lp(a), when expressed as a function of cholesterol concentration and measured in the same subject. The addition of beta-carotene to Lp(a) in vitro partially protected Lp(a) against oxidation and aggregation. As a result, uptake of oxidized Lp(a) by macrophages decreased markedly. We conclude that Lp(a) particles are prone to oxidation and that the increased risk of coronary artery disease associated with elevated Lp(a) levels may be related in part to their oxidative modification and uptake by macrophages, resulting in the formation of macrophage-derived foam cells.

Adult↗
PubMed1992

Probucol protects lipoprotein (a) against oxidative modification.

Probucol, which decreases cholesterol levels and has antioxidant properties, was administered orally to patients with familial combined hyperlipidemia and high plasma lipoprotein(a) [Lp(a)] levels. The drug had no effect on Lp(a) concentrations after 4 weeks, but was found to be distributed in both Lp(a) and low-density lipoprotein (LDL). Before treatment, in each case LDL and Lp(a) isolated from the same individual were readily oxidized by copper, resulting in increased electrophoretic mobility and enhanced uptake and degradation by macrophages of both lipoproteins. After probucol treatment, both lipoproteins acquired resistance to in vitro oxidation by copper. Furthermore, probucol prevented their enhanced uptake and degradation by the macrophages. It is surmised that oxidized Lp(a) may carry an atherogenic potential that could be opposed by probucol administration.

Adult↗
PubMed1990

Abnormal low density lipoproteins composition in some chronic alcoholics: a possible mechanism.

Decreased plasma low density lipoproteins (LDL) cholesterol and apolipoprotein B (apo B) levels are observed in heavy alcohol drinkers. LDL composition was determined in 16 alcohol addicts immediately after a period of alcohol abuse. Cholesterol to apo B ratio in the LDL fraction was significantly higher in the alcoholic group when compared with controls. In half of them the ratio exceeded 1.75. LDL subfractionation showed that in all subjects with atypically high LDL cholesterol to apolipoprotein B ratio, most of the LDL was in the form of a light subfraction. Acetylation in vitro showed that the heavy LDL subfraction was modified to a greater extent than the light subfraction. This suggests that the low apo B levels often observed after heavy drinking may arise from enhanced removal of the heavy LDL subfraction from the bloodstream.

Acetaldehyde↗
PubMed1989

Modification of low density lipoproteins from hypertriglyceridemic patients by macrophages in vitro and the effect of bezafibrate treatment.

After 30 days of bezafibrate administration to 5 patients with hypertriglyceridaemia and hyperapobetalipoproteinaemia a rise was found in the concentrations of cholesterol and vitamin E in the LDL fraction. In consequence the susceptibility of the LDL fraction to oxidation by macrophages was reduced. The uptake of modified LDL by these cells was decreased in relation to the uptake before treatment.

Adult↗
PubMed1987

Influence of bezafibrate and colestipol on LDL-cholesterol, LDL-apolipoprotein B and HDL-cholesterol in hyperlipoproteinaemia.

A significant increase of LDL-apolipoprotein B by 13% and LDL-cholesterol by 19% was observed in a group of 9 patients with hyperlipoproteinaemia Type III after bezafibrate treatment. Additional administration of colestipol caused a significant decrease of both LDL-apolipoprotein B by 18% and LDL-cholesterol by 25%. In 10 patients of hyperlipoproteinaemia Type IIb a significant decrease of both LDL-apolipoprotein B by 28% and LDL-apolipoprotein B by 18% was observed after bezafibrate therapy. When bezafibrate was given together with colestipol a further decrease of both LDL-cholesterol by 17% and LDL-apolipoprotein B by 16% occurred. HDL-cholesterol concentration increased significantly in both groups of hyperlipaemic patients during therapy. This may be the effect of both bezafibrate and colestipol. It is concluded that bile acid resins may effectively prevent the LDL-cholesterol concentration increase observed sometimes after clofibrate analogues.

Adult↗
PubMed1987

The effect of thermally oxidized soya bean oil on metabolism of chylomicrons. Increased uptake and degradation of oxidized chylomicrons in cultured mouse macrophages.

Oral administration of thermally oxidized soya bean oil (TO) increased the level of lipid peroxides in human plasma, mainly in chylomicrons. No changes were observed after fresh oil (FO) intake. Human chylomicrons obtained after TO ingestion were rich in lipid peroxides and degraded more rapidly by cultured mouse macrophages than chylomicrons after FO. The uptake of TO chylomicrons by macrophages occurred via a saturable process and was partially inhibited by beta-very low density lipoprotein as well as by acetyl-low density lipoprotein and fucoidin. A 48-h incubation of macrophages with TO chylomicrons caused a 10-fold higher accumulation of cholesterol ester mass in the cells than the incubation with FO chylomicrons. These studies suggest that chylomicrons containing lipid peroxides may be taken up by mouse macrophages by mediation of beta-VLDL receptor as well as by acetyl-LDL receptor, and show a potential pathway by which chylomicrons obtained after ingestion of heated oil could contribute to accumulation of cholesterol esters in macrophages.

Adult↗