Expression of different lipoprotein receptors in natural killer cells and their effect on natural killer proliferative and cytotoxic activity.

Natural killer (NK) cells take up chylomicrons (CM), very low density (VLDL), low density (LDL), high density (HDL) and acetyl-modified low density (AcLDL) lipoproteins through different receptors, VLDL being the lipoprotein with the highest uptake and HDL the lowest. The uptake of LDL can be selectively blocked by the anti-LDL receptor, which does not affect the uptake of CM, VLDL, HDL and AcLDL. Although the uptake of lipoproteins assessed by flow cytometry using DiI is not very high, the lipoproteins are able to induce an increase in proliferative responses, VLDL, AcLDL and HDL being the most important ones with 12- and 17-fold increments, respectively. CM, VLDL and LDL at low concentrations increase NK cytotoxic activity, while HDL and AcLDL inhibit, in a dose-dependent fashion, the killing of NK cells against K562. These results suggest the presence of four different receptors that are responsible for the cytotoxic and proliferative responses observed.     

Substrate specificity of plasma lecithin: cholesterol acyltransferase in abetalipoproteinemia

The lecithin: cholesterol acyltransferase (LCAT) activity of lipoprotein-depleted plasma from a patient with abetalipoproteinemia has been assayed in a modified Glomset-Wright incubation system with three different normal lipoprotein substrates consisting of an authentic mixture of very low (VLDL), low (LDL) and high (HDL) density lipoproteins for the assay of total LCAT activity, HDL to assay alpha-LCAT activity and combined VLDL and LDL to assay beta-LCAT activity, respectively. Although reduced to about half the normal control values, both alpha- and beta-LCAT activities were present in the patient's plasma. It has been shown earlier that secretion of LCAT is linked to that of VLDL, but since patients with abetalipoproteinemia cannot form either chylomicrons or VLDL, our results suggest that a secretion of these triglyceride-rich lipoproteins do not seem to be a prerequisite for a basal secretion of beta-LCAT.     

Association between coagulation factors VII and X with triglyceride rich lipoproteins.

The association between the concentration of different plasma lipoproteins and plasma factor VII (F VII) was analysed by isolating plasma very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) lipoproteins and assessing their in vitro interaction with F VII by immunoenzyme assay using peroxidase labelled anti-factor VII immunoglobulins to determine whether F VII coagulant activity is prognostic for cardiovascular mortality. F VII bound to triglyceride rich lipoproteins, the fixation being stronger on chylomicrons and VLDL fractions than on LDL fractions. In our experiments HDL did not bind to F VII. The fixation of coagulation factor X (FX) tested by the same method is comparable with that of F VII. The nature of this fixation seemed to arise from hydrophobic interaction as calcium was not necessary and the use of Tween 20 inhibited the interaction. The binding of factors VII and X was increased when lipids were previously treated by phospholipase C and the interaction seemed to be completely dependent on the lipid part of the lipoproteins. Hyrophobic fixation is a possible mechanism of interaction of plasma lipoproteins and F VII and X, and it may be of importance in the covariance of triglyceride concentrations and the activity of vitamin K dependent coagulation factors.     

Serum lipids and proteins in newborn infants in Ivory Coast

This study has permitted, from samples of the cord of 521 newborns in the Ivory Coast, to determine the average values of the following blood parameters: total proteins, total cholesterol, triglycerides, uric-acid, natrium, high density lipoproteins (HDL), very low density lipoproteins (VLDL), low density lipoproteins (LDL), HDL cholesterol (HDLC), VLDL cholesterol (VLDL-C), LDL cholesterol (LDLC), albumin, alpha 1, alpha 2, beta and gammaglobulins. Variations of the biochemical parameters in function of sex, social standard and races, as well as the correlations between the lipidic and protidic parameters were set forth.     

Alterations of apolipoprotein B metabolism in HIV-infected patients with antiretroviral combination therapy

BACKGROUND: Dyslipidemia (predominantly hypertriglyceridemia) is frequently seen in patients receiving antiretroviral combination therapy (ART). However, the underlying mechanisms and long-term risks (e.g., cardiovascular events) are still unclear. OBJECTIVES/METHODS: In 5 patients with ART-associated dyslipidemia, stable isotope labeled amino acid tracer (d3-Leu) kinetic analysis over 12 days was used to investigate the metabolism of apolipoprotein B-containing lipoproteins (very low density lipoproteins [VLDL]1, VLDL2, intermediate density lipoproteins [IDL] and low density lipoproteins [LDL]). Data were compared with those in 6 healthy normolipidemic controls. RESULTS: The patients under ART showed significantly increased fasting triglycerides (359 vs. 77 mg/dl) and VLDL (54 vs. 15 mg/dl), compared with controls. They had significantly higher total cholesterol (213 vs. 157 mg/dl) and there was a nonsignificant trend toward higher LDL (136 vs. 93 mg/dl), and toward lower HDL (26 vs. 46 mg/dl). The ratio of large, buoyant LDL1 over small, dense LDL2 was markedly reduced in patients under ART (0.80 vs. 2.00). Total apo B synthesis was significantly increased (25.5 vs. 14.5 mg/kg/d) and shifted toward triglyceride rich VLDL1 (18.5 vs. 8.7 mg/kg/d) in patients receiving ART. There was also a significantly reduced rate of apo B lipoprotein transfer from VLDL1 to VLDL2 (3.7 vs. 20.7 pools/d). In addition, all patients revealed insulin resistance. CONCLUSIONS: These data indicate that increased triglycerides in HIV-infected patients with ART are primary due to reduced rates of VLDL transfer into denser lipoproteins implying a lower rate of lipoprotein lipase-mediated delipidation. In addition, total apo B synthesis was increased and shifted toward triglyceride-rich VLDL1. Overall, this lipoprotein profile in patients with ART-associated dyslipidemia implies an increased risk for cardiovascular events.     

Characterization of triglyceride rich lipoproteins with very light density by ultracentrifugation and agarose gel electrophoresis using triglyceride- and cholesterol-staining

Hypertriglyceridemia is an independent risk factor for atherosclerosis. This risk is most likely due to accumulation of circulating triglyceride rich lipoproteins with heterogeneous particles. The identification and characterization of these triglyceride rich lipoproteins is important to detect abnormality of triglyceride metabolism. In the present study, we developed a new method that combines ultracentrifugation and agarose gel electrophoresis with triglyceride- and cholesterol-staining. We investigated 40 subjects with hypertriglyceridemia. Triglyceride rich lipoproteins with very light density were recovered in the aqueous fraction after ultracentrifugation (17,000 x g, 15 min). The lipoproteins recovered in the aqueous fraction contained chylomicrons, if present, their remnants, and light-VLDL (d <1.000 g/ml) containing apoB-100, but not normal VLDL (d <1.006 g/ml) and IDL. Triglyceride rich lipoproteins in the aqueous fraction were characterized by electrophoresis patterns of triglyceride- and cholesterol-staining. Forty patients with hypertriglyceridemia were separated into 8 groups according to their electrophoretic patterns. In lipoproteins recovered in the aqueous fraction from each group, the triglyceride level was correlated with the respective cholesterol level. In summary, a system using ultracentrifugation and agarose gel electrophoresis with triglyceride- and cholesterol-staining is useful for characterization of triglyceride rich lipoproteins and their remnants.     

Fractional Composition of Blood Serum Lipoproteins in Mice and Rats with Triton WR 1339-Induced Lipemia

We compared fractional composition of blood serum lipoproteins (LP) in female ICR mice and Wistar rats induced by single administration of a nonionic detergent Triton WR 1339 in doses of 300 and 500 mg/kg. Lipemia in animals of both species was characterized by a sharp increase in the concentration of cholesterol and, particularly, of triglycerides in blood serum lipoproteins by the 24th hour after administration of the detergent. We revealed a significant increase in the concentrations of atherogenic VLDL cholesterol (due to VLDL2), intermediate density lipoproteins, and LDL. These changes were more pronounced in rats. The model of lipemia can be used to study the role of fractional composition of lipoproteins and, particularly, of triglycerides in the pathogenesis of atherosclerosis. Moreover, this model holds much promise for evaluation of the efficiency of hypolipidemic drugs (statins and fibrates) in normalizing the increased level of atherogenic cholesterol of VLDL and LDL.     

Identification of lipid components of human serum lipoproteins involved in the inhibition of Sindbis virus infectivity,hemagglutination, and hemolysis

Summary Human serum high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) were isolated and tested for their ability to inhibit Sindbis virus infectivity, hemagglutination and hemolysis. VLDL and LDL produced a strong reduction on both viral infectivity on Vero cell monolayers and attachment and fusion with erythrocytes, whereas HDL appeared to be only a weak inhibitor. Lipid and protein components were extracted from each class of lipoproteins to identify the molecules responsible for the inhibiting activity. Only the lipid moiety was found to inhibit Sindbis virus biological activities. Among the individual lipid components of lipoproteins, neutral lipids (cholesterol, oleic acid and palmitic acid) and negatively charged phospholipids (phosphatidylserine and phosphatidylinositol) and glycolipids (GM 3 ganglioside and cerebroside sulphate) were able to neutralize the virus suggesting that either hydrophobic or electrostatic interactions are involved in the inhibition.     

Higher values of hepatic lipase activity in postmenopause: relationship with atherogenic intermediate density and low density lipoproteins

OBJECTIVE: To investigate the enzymatic activity of hepatic lipase (HL) in postmenopausal women (PMW) and reproductive age women (RAW); and to evaluate the relationship between this enzyme and the atherogenic intermediate density lipoproteins (IDL) and low density lipoproteins (LDL), and antiatherogenic high density lipoproteins (HDL) and its subfractions (HDL2 and HDL3). DESIGN: We studied 55 PMW receiving no hormonal treatment in a cross-sectional study in comparison with a control group of 55 RAW, matched by body mass index. Follicle-stimulating hormone was > 40 mUI/ml in PMW and 3-12 mUI/ml in RAW. PMW presented at least 1 year of natural menopause and no more than 10 years of amenorrhea with E2 serum concentration < 15 pg/ml. RESULTS: HL activity was significantly higher in PMW versus RAW (14.0 +/- 1.4 vs. 10.9 +/- 0.4 micromol of fatty acids/ml of postheparin plasma, respectively, mean +/- SEM, p < 0.001). In PMW, IDL cholesterol showed a positive correlation with LDL cholesterol (r = 0.28, p < 0.05), and HDL2 cholesterol was inversely correlated with HL activity (r = 0.31, p < 0.05). HL was positively correlated with plasma concentration of LDL cholesterol in both groups (r = 0.27, p < 0.05). The higher values of HL activity and IDL cholesterol were independent of age. CONCLUSIONS: Higher HL activity is associated with a more atherogenic profile in PMW.     

Lipid changes in the nephrotic syndrome: New insights into pathomechanisms and treatment

Summary The abnormalities of lipid metabolism in nephrotic syndrome consist in an increase in total and low-density lipoprotein (LDL) cholesterol, apoliproteins B (ApoB), C-II and C-III, associated in patients with heavier or marked hypoalbuminemia with an increase in triglycerides and very low-density lipoprotein (VLDL) cholesterol, while the high-density lipoproteins (HDL) are distributed abnormally (increased HDL3 fraction and decreased HDL2 fraction) and the Apo A-I to Apo B ratio is reduced. Both increased hepatic lipoprotein synthesis and reduced removal capacity contribute to this hyperlipidemia. Proteinuria may lead to the lipoprotein abnormalities through stimulation of VLDL synthesis by the liver induced by hypoalbuminemia, although it has been more recently suggested that urinary protein loss is associated with the urinary loss of some important cofactor for the regulation of lipid synthesis or catabolism.Treatment of lipid abnormalities in patients with long-lasting heavy proteinuria is mandatory, because they may cause or contribute to accelerated atherosclerosis, but also because they appear to accelerate progression of renal disease by favouring mesangial sclerosis. Four groups of lipidlowering drugs have been tested: 1) bile acid-binding resins; 2) fibric acid; 3) probucol; 4) inhibitors of HMG CoA reductase. The drugs of the last group appear to be effective and safe in short-term experiments, but long-term studies are necessary to confirm their validity. A dietary approach, consisting in a strictly vegetarian soy diet, very rich in polyand monounsaturates fatty acids, has been recently tested by the author, with very promising results.Abbreviations LDL low density lipoproteins - VLDL very low density lipoproteins - HDL high density lipoproteins - Apo Apolipoprotein - LCAT Lecithin cholesterol acyltransferase - HMGCoA Hydroxymethylglutaryl coenzyme A Preprint of a lecture to be read at the 22nd Congress of the Gesellschaft für Nephrologie, Heidelberg, September 15–18, 1991 (Editor: Prof. Dr. E. Ritz, Heidelberg)     

Evidence for the presence in human plasma of lecithin: cholesterol acyltransferase activity (beta-LCAT) specifically esterifying free cholesterol of combined pre-beta- and beta-lipoproteins. Studies of fish eye disease patients and control subjects

The present study was undertaken to test our hypothesis that two different lecithin: cholesterol acyltransferase (LCAT) activities exist in normal human plasma, one denoted alpha-LCAT esterifying the free cholesterol of high density lipoproteins (HDL) and the other denoted beta-LCAT acting on the free cholesterol of very low (VLDL) and low (LDL) density lipoproteins. Plasmas depleted of HDL were obtained by means of preparative ultracentrifugation. Incubation at 37 degrees C of these plasma fractions from control subjects and patients with fish eye disease resulted in esterification of the remaining free cholesterol of combined VLDL and LDL (pre-beta- and beta-lipoproteins) in the HDL depleted plasmas. The shapes of the cholesterol esterification rate curves were similar for whole and HDL depleted plasmas from both control subjects and fish eye disease patients. In crosswise mixed incubation experiments with isolated combined VLD and LDL and total lipoprotein depleted plasma from a control subject and a patient with fish eye disease, respectively, esterification of free cholesterol occurred. Incubation of isolated total lipoproteins in plasma from a patient with LCAT deficiency mixed with total lipoprotein depleted plasma from a fish eye disease patient as a source of LCAT caused cholesterol esterification but did not result in normalization of the LCAT deficiency HDL particles, while the amount of normal-sized LDL particles increased. The present results support the hypothesis that a beta-LCAT exists in normal human plasma.     

Low-density lipoproteins isolated from the blood of patients with coronary heart disease induce the accumulation of lipids in human aortic cells

Smooth muscle cells cultured from the intima of unaffected human aorta accumulate lipids during incubation with the blood serum of patients with coronary heart disease (CHD). Blood sera of most healthy subjects fail to induce the deposition of lipids in cultured cells. Very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins of two subclasses (HDL2 and HDL3) were isolated from the blood of healthy subjects and CHD patients. LDL from the blood of healthy individuals did not raise intracellular lipid levels within 24 hr of cultivation (the maximal concentration used, 1000 micrograms/ml). During the same incubation period, LDL obtained from the blood of CHD patients (200 to 1000 micrograms/ml) caused a 2- to 5-fold rise in cholesteryl esters as well as a 1.5- to 3-fold rise in free cholesterol and triglycerides, whereas intracellular phospholipid levels remained unchanged. There was a direct correlation (r = 0.95) between cholesterol accumulation in the cells incubated with whole sera of CHD patients and cholesterol level in the cells incubated with LDL isolated from these sera. In one of the three cases, the ability to raise the intracellular level of cholesteryl esters was demonstrated by VLDL (500 micrograms/ml) derived from CHD patients' blood. HDL2 and HDL3 did not affect lipid levels in smooth muscle cells cultured from unaffected intima. HDL3 from the blood of CHD patients and healthy subjects (50 to 250 micrograms/ml) reduced cholesteryl ester levels in cells cultured from atherosclerotic plaques 1.5- to 2-fold. HDL2 also decreased the content of cholesteryl esters in plaque cells, though less effectively than HDL3. The data obtained suggest that circulating LDL and, possibly, VLDL in the blood of CHD patients are capable of inducing the accumulation of fat in vascular wall cells.     

Deficiency of hepatic lipase activity in post-heparin plasma in familial hyper-alpha-triglyceridemia

Hyper-alpha-triglyceridemia is a rare dyslipoproteinemia characterized by a pronounced increase in the concentration of triglycerides in the plasma high density lipoprotein (HDL) fraction. One case with this condition, an apparently healthy 61-year-old man, has been studied. Additional lipoprotein abnormalities were present, such as abnormally cholesterol-rich very low density lipoproteins (VLDL) with retarded electrophoretic mobility (beta-VLDL) and triglyceride enrichment of low density lipoproteins (LDL). The patient's plasma concentration of apolipoproteins A-I, A-II and B were normal and those of C-I, C-II, C-III and E were elevated. No abnormal forms of the soluble apolipoproteins of VLDL and high density lipoproteins (HDL) were found after analysis by isoelectric focusing. Lecithin:cholesterol acyltransferase activities, plasma cholesterol esterification rates and lipid transfer protein activities were normal. Post-heparin plasma activity of hepatic lipase was virtually absent and that of lipoprotein lipase was reduced by 50%. In plasma of this patient, HDL was almost exclusively present as large triglyceride-rich particles corresponding in size to particles of the HDL2 density fraction. The only brother of the patient also had hyper-alpha-triglyceridemia together with the other lipoprotein abnormalities described for the index case and deficiency of postheparin plasma activity of hepatic lipase. The findings presented below support the hypothesis that one primary function of hepatic lipase is associated with degradation of plasma HDL2. Deficiency of this enzyme activity thus causes accumulation of HDL2 in plasma leading to hyper-alpha-triglyceridemia. The results further suggest that the abnormal chemical and electrophoretic properties of VLDL and LDL in plasma from the patient, reminiscent of type III hyperlipoproteinemia, are secondary to the lack of the action of hepatic lipase on the HDL particles.     

Possible involvement of very low density lipoproteins in steroidogenesis in the human ovary

To determine whether human luteal cells can utilize very low density lipoproteins (VLDL)-carried cholesterol for steroidogenesis, we investigated the expression of VLDL receptor mRNA in human ovarian tissues and progesterone production by human luteinized granulosa cells after the addition of VLDL. The production of progesterone in the presence of human chorionic gonadotrophin (HCG) was increased significantly (P < 0.05) by VLDL (2479 +/- 1477 ng/10(5) cells, mean +/- SD, n = 6) and low density lipoproteins (LDL) (2726 +/- 1287), in comparison with the level in the absence of these lipoproteins (1350 +/- 739). Northern blot analysis revealed that the levels of expression of VLDL and LDL receptor mRNA in granulosa cells were almost equal to those in whole ovarian tissue. VLDL receptor mRNA was abundant in granulosa cells of preovulatory follicles and cells of the corpus luteum. Preovulatory thecal cells and stromal cells expressed lower amounts of VLDL receptor mRNA than granulosa cells of preovulatory follicles and cells of the corpus luteum. From the present study, it might be suggested that VLDL is utilized for steroidogenesis in human luteinized granulosa cells.      

Lipoproteins in human atherosclerotic vessels. I. Biochemical properties of arterial low density lipoproteins, very low density lipoproteins, and high density lipoproteins.

Lipoproteins extracted from the human aortic intima into 1.65 M NaCl were quantitated and characterized biochemically and by electron microscopy following separation in the preparative ultracentrifuge. The arterial lipoproteins, although separated and designated according to the density classes used for the serum lipoproteins, were distinctly different from their serum counterparts. The amount of lipoproteins in the low density range of d 1.063 to 1.006 (arterial LDL) and in the very low density range of d < 1.006 (arterial VLDL) extracted from arterial intima increased with increasing intimal lipid content. In contrast, the concentration of lipoproteins in the high density range of d 1.210 to 1.063 (arterial HDL) was small and did not change with the severity of atherosclerosis.Arterial VLDL, LDL and its subfractions, LDL₁ (d 1.006 to 1.019) and LDL₂ (d 1.019 to 1.063), were markedly heterogenous and contained unusually large particles, which were isolated by Bio-Gel A-150. These particles showed a pitted and cratered appearance by scanning electron microscopy and were immunochemically unreactive and had no electrophoretic mobility. The lipid and amino acid composition of the arterial VLDL and LDL fractions as well as their electrophoretic, chromatographic and analytical flotation behavior was distinctly different from that of their serum lipoprotein counterparts. Arterial VLDL, in sharp contrast to serum VLDL, was rich in cholesteryl ester and poor in triglycerides. Arterial VLDL also showed no electrophoretic mobility and only half of the preparations reacted to LDL antisera. Acid mucopolysaccharides were detected in the arterial VLDL and LDL fractions in association with the large size particles which lacked electrophoretic mobility and immunochemical reactivity and showed only a “saw tooth” pattern in the analytical ultracentrifuge. Arterial LDL and LDL₂ contained a smaller sized population of particles as separated by Bio-Gel A-150. These particles exhibited a reaction of complete identity with serum LDL when reacted against LDL antiserum. However these particles had a greater electrophoretic mobility and different amino acid composition than did serum LDL and LDL₂. An asymmetrical peak with a mean SF of 7.3 was demonstrated by these particles in the analytical ultracentrifuge.The over-all studies suggest that lipid deposition in atherosclerotic plaques is associated with the accumulation of lipoproteins with biochemical and ultrastructural properties unlike those of serum lipoproteins. The presence of these lipoproteins in the arteries may be a result of the interaction of serum and arterial lipoproteins with acid mucopolysaccharides and of lipoprotein synthesis and degradation in the arteries.     

Evaluation of the classical methods for the diagnosis of type III hyperlipoproteinemia

Summary Familial type III hyperlipoproteinemia is characterized by the presence of elevated plasma levels of very low density lipoproteins (VLDL) which contain an increased amount of cholesterol and by the presence of a significant amount of lipoproteins with an intermediate density between that of VLDL and low density lipoproteins (LDL); the intermediate density lipoproteins, designated IDL or Lp III, have a slower electrophoretic migration rate than VLDL, and are found in the ultracentrifugal top fraction as a contaminant. Classically, the diagnosis of type III is based on the demonstration of beta-migrating lipoproteins in the ultracentrifugal top fraction (density <1.006), thus floating beta-lipoprotein. More recently, it has been proposed that an elevated VLDL-cholesterol to triglyceride ratio is diagnostic of the disorder. In the present report, we have compared the two methods for their diagnostic value and have concluded that the chemical index definition is the more reliable method for the diagnosis of type III hyperlipoproteinemia.     

Die Wirkungen gleicher Mengen Linolsäure in oral zugeführten,mehrfach ungesättigten Phospholipiden oder in Safloröl auf die Lipoproteine des Plasmas

Summary The effects of polyenylphosphatidylcholine in a dosage of 10 g per day were compared with an equimolar amount of linoleic acid in 7 g safloroil per day in 8 healthy subjects for 3 weeks. The concentrations of cholesterol, triglycerides, phospholipids, apolipoproteins A-I, A-II and B were measured in serum, as well in VLDL, LDL, HDL, HDL₂, HDL₃ on the day before, after 2 and 3 weeks of application and 6 months after the experiment. The diet was controlled 10 days before and during the experiment using the dietary recall method. According to the dietary records there was an increase of fat supply during application of polyenylphosphatidylcholine inhibiting decrease of LDL cholesterol, which was observed with safloroil. Phospholipid concentrations increased significantly with polyenylphosphatidylcholine in VLDL. Apolipoprotein B in LDL was significantly decreased by both substances. Apolipoprotein A-I and A-II in HDL increased significantly with polyenylphosphatidylcholine. With safloroil this effect was limited to apolipoprotein A-I, but less impressive. The effects of both substances are comparable in the decrease of apolipoprotein B and probably cholesterol. A special effect of polyenylphosphatidylcholine was observed on phospholipids in VLDL and on apolipoprotein A-I and A-II in HDL.

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Abkürzungen PPC Polyenylphosphatidylcholin - VLDL Very low density lipoproteins - LDL Low density lipoproteins - HDL High density lipoproteins - LCAT Lecithin-Cholesterin-Acyl-Transferase     

The relationship between serum lipids,nucleation time,and biliary lipids in patients with gallstones

Summary The relationship between biliary lipids, cholesterol saturation index, nucleation time, and serum lipids was studied in a group of 45 gallstone patients (10 male, 35 female; age 50.1 ±14.5 years). Bile was obtained by direct fine-needle puncture of the gallbladder under local anesthesia and sonographic monitoring. No significant correlation between the serum lipids and either the cholesterol saturation index or total biliary cholesterol levels was observed. We found a positive correlation between the nucleation time and serum triglycerides content (r = 0.45, p = 0.0018) and a negative correlation between nucleation time and biliary cholesterol level (r = –0.38, p = 0.009). The fatty acids derived from the triglycerides are primarily resynthesized to phospholipids in the liver. When the supply of free fatty acids exhausts the metabolic capacity of the liver as, for example, in fat-rich diets, triglycerides accumulate in the liver cells and may possibly be excreted in the bile. Free fatty acids stimulate mucin hypersecretion in the gallbladder. This mucosal hypersecretion has been assigned a significant role in the formation of gallbladder stones. We also found a positive correlation between the total biliary bile acids and serum high density lipoprotein (HDL)-cholesterol in patients with a rapid nucleation time (r = 0.50, p = 0.0128). This supports the findings of other researchers, which suggests that HDL-cholesterol is devoted primarily to bile acid synthesis. In patients with a short nucleation time, the cholesterol saturation index, total lipid concentration, biliary cholesterol, mean age, and biliary bile acids were statistically different in comparison with patients with a prolonged nucleation time.Abbreviations CSI cholesterol saturation index - CT computer tomography - HU Hounsfield units - NT nucleation time - TLC total lipid concentration - LDL/HDL low/high density lipoproteins - VLDL very low density lipoproteins     

XbaI polymorphism of apolipoprotein B gene in a Tunisian population: alleles frequencies and relationship with plasma lipid parameters

Apolipoprotein B (Apo B) is a component of chylomicrons, low-density lipoproteins (LDL), very low density lipoproteins (VLDL), and intermediate-density lipoproteins (IDL) and is the ligand for the LDL receptor. Thereby, Apo B plays a central role in lipoprotein metabolism and in maintaining the normal homeostasis of serum cholesterol levels. Several Apo B restriction fragment length polymorphisms (XbaI, EcoRI, MspI) have been reported to be associated with variation in lipid levels, obesity and/or coronary artery disease. To date, no data are available on relationship between XbaI Apo B polymorphism and lipid levels in Tunisian population. Here, we report frequencies of the XbaI polymorphism of the Apo B gene and we assess the effect of this polymorphism on lipid and lipoprotein concentrations in Tunisian population. Blood samples from 296 Tunisian individuals (112 women and 184 men, aged 51.4+/-9.6 years), were analysed for total cholesterol, triglycerides, HDL-cholesterol and apolipoproteins A1 and B. In parallel, genotyping by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was performed. The XbaI polymorphism was associated with differences in plasma cholesterol (p=0.04), triglyceride (p=0.02) and apolipoprotein A1 (p=0.004), individuals with the genotype X1X1 have the lowest mean levels and those with the genotype X2X2 have the highest, with the individuals heterozygous for the polymorphism having intermediate levels. According to sex, the XbaI polymorphism effect was only observed for triglyceride in men. Thus, the results demonstrate an influence of XbaI polymorphism of Apo B gene on serum total-cholesterol, triglycerides and apolipoprotein A1 concentrations among Tunisian population.     

Altered lipoprotein composition and elevated serum lipids in chicken embryos with hereditary muscular dystrophy

The earliest biochemical changes reported in chickens with hereditary muscular dystrophy are increased cholesterol levels in liver, serum and pectoral muscles at 9 days of embryonic development. We have investigated whether there were concomitant differences in serum lipoprotein composition (VLDL, very low density lipoproteins; LDL, low density lipoproteins; HDL high density lipoproteins)**, and levels of serum triglycerides (TG), free cholesterol (FC) and cholesteryl esters (CE) in normal chicken embryos and in those with hereditary muscular dystrophy between 10 and 16 days in ovo. VLDL and CE content of the serum of dystrophic embryos are significantly elevated compared to those of the normal serum from 10 to 16 days in ovo, and serum TG is significantly increased at 12 and 14 days in ovo. Serum LDL and HDL concentrations are significantly lower in dystrophic embryos at 14, 16 and 12 days respectively. It is proposed that an increased rate of CE synthesis, probably in the liver, induces the formation of CE-rich, TG-poor VDLD-like lipoprotein. Decreased degradation of this lipoprotein by peripheral tissues, especially muscles, may account for the high VLDL levels in the dystrophic embryos. Since dystrophic chickens exhibit hyperlipoproteinemia followed by muscle degeneration, this disease has features in common with human spinal muscular atrophy.