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Biomedical subjects

I Beucler

Publications and source records attributed to I Beucler.

At least 19 recordsLinked to original sources

Blood oxidative stress markers are unreliable markers of hepatic steatosis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and viral hepatitis are associated with hepatic oxidative stress, which is partially dependent on the amount of hepatic fat. AIM: To determine whether the circulating lipid and oxidative stress parameters could be non-invasive markers of hepatic steatosis. METHODS: Sixty-four patients with NAFLD or viral hepatitis were tested for lipid peroxidation products and antioxidant defence systems, lipid parameters and liver function tests. RESULTS: Hepatic steatosis was correlated with lipids, gamma-glutamyltranspeptidase, thiobarbituric acid-reactive substances, superoxide dismutase and superoxide dismutase/erythrocyte glutathione peroxidase ratio. gamma-Glutamyltranspeptidase, triglycerides and low-density lipoprotein cholesterol were significantly higher in the presence of steatosis. No difference in blood oxidative stress markers was observed according to the presence or absence of steatosis except for the superoxide dismutase/erythrocyte glutathione peroxidase ratio. Total cholesterol, triglycerides and low-density lipoprotein cholesterol were significantly higher in the NAFLD group (n = 17, 60% mean steatosis grade) than in the viral hepatitis group (n = 20, 13% mean steatosis grade). Only superoxide dismutase was lower and vitamin E higher in NAFLD than in viral hepatitis patients. CONCLUSIONS: Standard blood oxidative stress markers do not predict the extent of hepatic steatosis as they probably do not accurately reflect intrahepatic oxidative stress. Serum lipid levels were best correlated with hepatic steatosis.

Adult↗

APOE: a potential marker of disease progression in ALS.

Although documented in AD, the role of APOE remains unclear in ALS. APOE phenotype and plasma levels were measured in 403 patients with ALS and were correlated with clinical parameters and survival time. No correlations were observed between the APOE phenotype and these variables. In contrast, APOE plasma levels were correlated with both rate of deterioration and survival time and appeared to be an important risk factor for decreased survival time with a relative risk of 0.647 (95% CI: 0.465 to 0.901; p = 0.01).

Adult↗

Smaller LDL particle size in women with polycystic ovary syndrome compared to controls.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease. The contribution of lipid abnormalities to this higher risk, in particular atherogenic modifications of low density lipoprotein (LDL) such as a shift towards smaller LDL, has not been properly explored. We aimed to examine LDL size variation in relation to androgens and other risk factors in women with PCOS. DESIGN: Comparison of clinical and biochemical measurements in women with PCOS and women with normal ovarian function, of similar age and body mass index (BMI). PATIENTS: Thirty-one women with PCOS and 27 controls were studied. Patients were recruited from the outpatient endocrine clinic. MEASUREMENTS: Fasting total cholesterol, triglycerides (TG), high density lipoprotein (HDL), LDL, glucose, insulin, gonadotrophins, androgens, oestradiol, 17 OH progesterone and SHBG were measured. LDL particle diameter was calculated based on distance travelled in polyacrylamide native gels. Recumbent blood pressure was measured automatically. RESULTS: LDL particle size appeared to be significantly smaller in hyperandrogenic PCOS as compared to regularly cycling women (P = 0006), independent of variations in lipid levels. SHBG was the only independent predictor of LDL size in this population, with a strong correlation, which persisted after adjustment for all confounding variables. CONCLUSIONS: Our results suggest that androgen excess and mild insulin-resistance (both responsible for lower SHBG) may have an early modifying effect on low density lipoprotein size in polycystic ovary syndrome women. The denser pattern observed in polycystic ovary syndrome women could by itself constitute a higher cardiovascular risk, even in the absence of overt dyslipidaemia, and contribute to the excess risk of cardiovascular disease reported in this syndrome.

Adult↗

Plant sterol-enriched margarine lowers plasma LDL in hyperlipidemic subjects with low cholesterol intake: effect of fibrate treatment.

Phytosterols, found in fat-soluble fractions of plants, chemically resemble cholesterol and inhibit cholesterol absorption in the small intestine. Phytosterol consumption in human subjects reduces plasma total and low density lipoprotein-cholesterol (LDL-C) levels. The primary aim of this study was to determine the efficacy of a low-fat spread enriched with plant sterols in reducing total and LDL-C concentrations in primary hypercholesterolemia. The secondary objective was to evaluate whether patients receiving a lipid-lowering drug (fibrate) might differ in their response to plant sterols. The study was a randomized, double-blind, placebo-controlled two-period cross-over trial with two treatments and three periods. Both treatment periods lasted 2 months, with a washout period (2 months) between them. Spread enriched with plant sterols was compared to non-enriched control spread. Fortified fat spread provided 1.6 g/day of plant sterols derived from edible vegetable oils and fatty acids from sunflower seed oil. The plant sterol content consisted of sitosterol esters (50%), campesterol esters (25%), stigmasterol esters (20%) and 10% of other esters. Data in 53 hypercholesterolemic patients (31 females and 22 males) who completed the study were as follows: patients were 58+/-12 years of age with mean body mass index 23.5+/-2.8 kg/m2 (mean+/-SD). No adverse side-effects of the diet were reported. Plasma total cholesterol and LDL-C concentrations were significantly reduced by 6.4% and 8.8%, respectively, after using the spread enriched in plant sterols, as compared to controls (0.0% and 1.3%, respectively). No effect on high density lipoprotein-cholesterol (HDL-C) and lipoprotein(a) concentrations was detected. When subjects were divided in two subgroups according to fibrate treatment, supplementation with phytosterols decreased plasma cholesterol and LDL-C by 8.5% and 11.1%, respectively in the subgroup of patients treated with fibrates. In the group of patients who did not receive fibrates, consumption of plant sterol margarine reduced plasma cholesterol and LDL-C by 5.5% and 7.7%, respectively. Spread enriched with plant sterol esters significantly lowers blood total and LDL-C levels without affecting HDL-C concentrations, in a hypercholesterolemic population following a strict low cholesterol diet (NCEP step1). In addition, a combination of fibrate treatment and plant sterol ester-supplemented spread offers a safe and effective measure to significantly decrease abnormally high cholesterol levels. We conclude that phytosterol-enriched spread is a useful adjunctive therapy for hypercholesterolemic patients.

Adult↗

[Metabolism of atherogenic lipoproteins].

Early development of atherosclerosis results from a complex multifactorial process where lipoprotein anomalies play a predominant role. The metabolism of lipoproteins is regulated by numerous reactions between the structural components of the lipoproteins and the receptors and/or enzymes with which they interact. Among the well-characterized anomalies, the elevation of small and dense LDL and/or the diminution of HDL levels are in first line of the factors involved in the formation of atheromatous plaques. LDL play a direct role by penetrating the intima of the arteries and HDL play an reverse transport of cholesterol from cells to the liver. There has been a long debate concerning risk related to triglyceride rich lipoproteins (TGRL), and more particularly the increase in VLDL. However, a large number of studies have demonstrated that these ephemeral lipoproteins can acquire major atherogenic potential when their level is increased and/or they are associated with perturbed metabolism leading to an accumulation of remnants. Current investigation methods have shown that LDL and HDL-cholesterol levels are excellent markers of LDL and HDL concentrations. Inversely, triglyceride levels provide little information concerning the nature of the elevated TGRL and fasting hypertriglyceridemia, even if moderate, should therefore be considered as a warning sign of persistent atherogeneous remnants in the fasting state.

Arteriosclerosis↗

Changes in lipoprotein(a) levels and hormonal correlations during a weight reduction program.

BACKGROUND AND AIM: To examine the effects of a weight reduction program on serum lipoprotein(a) [Lp(a)] levels and investigate whether the hormonal modifications occurring during weight loss may explain the changes in Lp(a) levels. METHODS AND RESULTS: This longitudinal clinical intervention study of a low-calorie diet involved 62 healthy obese patients (21 men aged 32 +/- 9.6 years and 41 women aged 37 +/- 14.6 years). Their anthropometric parameters (weight, height, body mass index, waist-to-hip ratio), fasting serum lipid levels, hormones (total testosterone, estradiol, total triiodothyronine, insulin), sex hormone binding globulin (SHBG) and blood sugar levels were determined at baseline and after six weeks of dietary treatment. A 7.5% loss in initial body weight was achieved and there was a statistically significant decrease in serum total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides (p < 0.001). No changes in Lp(a) levels were observed in the study population as a whole, but there was a 17.6% (p < 0.05) reduction in the subjects with high pre-treatment Lp(a) values (> 20 mg/dL). The decrease in Lp(a) levels closely correlated with initial Lp(a) levels (r = 0.81 p < 0.001), but did not correlate with changes in anthropometric parameters or the hormonal modifications occurring during the weight loss. CONCLUSIONS: A low-calorie diet associated with weight loss in obese subjects may have beneficial effects on serum Lp(a) levels in patients with high pre-treatment Lp(a) concentrations. This effect seems to be independent of the hormonal changes observed during weight loss.

Adult↗

Usefulness in predicting coronary artery disease by ultrasonic evaluation of the carotid arteries in asymptomatic hypercholesterolemic patients with positive exercise stress tests.

A positive exercise electrocardiogram (ECG) is not infrequent occurrence in asymptomatic hypercholesterolemic patients, but the number of false-positive tests may be relatively high (50%). Therefore, the ability of a positive stress ECG to predict coronary artery lesions is low even in populations with > or =1 cardiovascular risk factors. To increase the diagnostic value of exercise tests for screening asymptomatic individuals, we analyzed whether combined clinical parameters with carotid echography would accurately predict coronary atherosclerotic lesions by coronary angiography in asymptomatic hypercholesterolemic patients with a positive exercise ECG. Seventy-six asymptomatic patients (between 35 and 65 years of age) with hypercholesterolemia (total plasma cholesterol >6.5 mmol/L or 250 mg/dl) and a positive stress ECG were referred for carotid B-mode echography and coronary angiography. Carotid echography data were divided into 2 categories: (1) absence of any atherosclerotic plaque, or (2) presence of > or =1 arterial plaques. Coronary stenosis assessed by coronary angiography was considered to correspond to a > or =50% reduction of coronary lumen diameter. Forty-three patients (57%) displayed coronary lesions; most (38; 88%) had carotid plaque. Multivariate analysis showed that the presence of carotid plaque was significantly associated with coronary stenosis (odds ratio 15.2; confidence interval 5.0 to 54.5). In subgroups characterized by high frequency of false-positive exercise electrocardiographic tests (women and patients with a 10-year predicted risk of coronary artery disease [CAD] <15%), none of the patients without carotid plaque exhibited coronary lesions. Echographic evaluation of carotid plaque (plaque vs no plaque) significantly improved the diagnostic specificity of exercise electrocardiography. We conclude that the combination of clinical, electrical, and echographic data facilitates cost-effective noninvasive detection of CAD in asymptomatic hypercholesterolemic patients.

Carotid Arteries↗

Interrelationships between postprandial lipoprotein B:CIII particle changes and high-density lipoprotein subpopulation profiles in mixed hyperlipoproteinemia.

We studied the relationships postprandially between triglyceride-rich lipoprotein (TRL) and high-density lipoprotein (HDL) in 11 mixed hyperlipoproteinemia (MHL) and 11 hypercholesterolemia (HCL) patients. The high and prolonged postprandial triglyceridemia response observed in MHL but not HCL patients was essentially dependent on very-low-density lipoprotein (VLDL) changes. This abnormal response was related to decreased lipoprotein lipase (LPL) activity (-48.7%, P<.01) in MHL compared with HCL subjects. Cholesteryl ester transfer protein (CETP) activity was postprandially enhanced only in MHL patients, and this elevation persisted in the late period (+19% at 12 hours, P<.05), sustaining the delayed enrichment of VLDL with cholesteryl ester (CE). The late postprandial period in MHL patients was also characterized by high levels of apolipoprotein B (apoB)-containing lipoproteins with apoCIII ([LpB:CIII] +36% at 12 hours, P<.01) and decreased levels of apoCIII contained in HDL ([LpCIII-HDL] -34% at 12 hours, P<.01), reflecting probably a defective return of apoCIII from TRL toward HDL. In MHL compared with HCL patients, decreased HDL2 levels were related to both HDL2b and HDL2a subpopulations (-57% and -49%, respectively, P<.01 for both) and decreased apoA-I levels (-53%, P<.01) were equally linked to decreased HDL2 with apoA-I only (LpA-I) and HDL2 with both apoA-I and apoA-II ([LpA-I:A-II] -55% and -52%, respectively, P<.01 for both). The significant inverse correlations between the postprandial magnitude of LpB:CIII and HDL2-LpA-I and HDL2b levels in MHL patients underline the close TRL-HDL interrelationships. Our findings indicate that TRL and HDL abnormalities evidenced at fasting were postprandially amplified, tightly interrelated, and persistent during the late fed period in mixed hyperlipidemia. Thus, these fasting abnormalities are likely postprandially originated and may constitute proatherogenic lipoprotein disorders additional to the HCL in MHL patients.

Adult↗

Characterization of two HDL subfractions and LpA-I, LpA-I:A-II distribution profiles and clinical characteristics of hyperalphalipoproteinemic subjects without cholesterol ester transfer protein deficiency.

The aims of the present study were (i) to characterize the HDL2, HDL3 and the LpA-I, LpA-I:A-II distribution, (ii) to investigate the prevalence of atherosclerotic lesions and (iii) to assess the activity of cholesteryl ester transfer protein (CETP) in 29 hyperalphalipoproteinemic (HALP) patients (HDL-C=90+/-11 mg/dl) with combined hypercholesterolemia (LDL-C=180+/-16 mg/dl). According to the HDL2/HDL3 and LpA-I/LpA-I:A-II ratios, two HALP profiles (A and B) were defined: in 22 patients (HALP profile A) these ratios were increased compared to the normolipidemic control subjects (1.19+/-0.11 versus 0.53+/-0.19, P < 0.001 and 1.01+/-0.2 versus 0.51+/-0.25, P < 0.001, respectively) and in seven patients (HALP profile B) these ratios were within the normal range (0.64+/-0.20 and 0.69+/-0.2, respectively). The atherosclerotic lesions were assessed by ultrasonography of the carotid arteries. Amongst patients with HALP profile A, 17 were free from lesions, five had intimal wall thickening and none displayed plaques, whereas for patients within the HALP profile B, only one was free from lesions, two had intimal wall thickening and four displayed plaques. CETP activities (348+/-116 versus 371+/-75%/ml/h) and CETP concentrations (2.4+/-0.5 versus 2.5+/-0.6 microg/ml) were similar in HALP profiles A and B, however these values were both higher than in control subjects (190+/-40%/ml/h, P < 0.001 and 1.8+/-0.3 microg/ml, P < 0.001, respectively). Hence the hyperalphalipoproteinemic profiles (A and B) described here were not related to CETP deficiency. In conclusion, the HALP profile A was characterized by both increased HDL2/HDL3 and LpA-I/LpA-I:A-II ratios and was associated with a low prevalence of atherosclerosis, whereas the HALP profile B, characterized by HDL2/HDL3 and LpA-I/LpA-I:A-II ratios within the normal range, was less cardioprotective.

Adult↗

Hyperalphalipoproteinemia: characterization of a cardioprotective profile associating increased high-density lipoprotein2 levels and decreased hepatic lipase activity.

The aim of the present study was to investigate the high-density lipoprotein (HDL) structural characteristics and metabolism in hyperalphalipoproteinemic (HALP) patients (HDL-cholesterol [HDL-C], 92 +/- 14 mg/dL) with combined elevated low-density lipoprotein-cholesterol (LDL-C) levels (LDL-C, 181 +/- 33 mg/dL). Patients were subjected to a complete cardiovascular examination, including ultrasonographic investigation of carotid arteries. Two HALP profiles were identified according to the HDL2/HDL3 ratio. HALP profile A was characterized in 28 patients by increased HDL2/HDL3 ratio, HDL2b, and lipoprotein (Lp)A-I levels compared with normolipidemic subjects, and HALP profile B, including the 12 remaining patients, was characterized by a HDL2/HDL3 ratio within the normal range and by the increase of all HDL subclasses (HDL(2b,2a,3a,3b,3c)), LpA-I, and LpA-I:A-II levels. With regard to the exploration of carotid arteries, in HALP profile A, 20 patients were free from lesions and eight had only intimal wall thickening. In HALP profile B, only one patient was free from lesions, four had intimal wall thickening, and seven displayed plaques, but none had stenosis. Taking into account the number of patients with plaques within each group, HALP profile A was associated with a low prevalence of atherosclerotic lesions, whereas HALP profile B was less cardioprotective (odds ratio, 77.7 [95% confidence interval, 3.7 to 1,569.7]; P < .0001). For both HALP profiles, cholesteryl ester transfer protein (CETP) deficiency was discarded and activities of phospholipid transfer protein (PLTP) and lipoprotein lipase (LPL) were normal. However, hepatic lipase (HL) activity was significantly decreased in HALP profile A, but within the normal range for HALP profile B. In conclusion, an HALP profile A with a low prevalence of atherosclerosis was characterized by an increased HDL2/HDL3 ratio, HDL2b, and LpA-I levels associated with decreased HL activity.

Adult↗

Rapid electrophoretic separation of pre-beta-migrating high density lipoproteins using automated PhastSystem: application to analysis of lecithin:cholesterol acyltransferase-deficient plasma.

To identify pre-beta-high density lipoproteins, a rapid two-dimensional separation by electrophoresis (1 hour 30 minutes) was performed on an automated Phast System. This procedure used commercially available polyacrylamide gradient gels (4-15%) and allows sensitive and reproducible results. Pre-beta-1- and pre-beta-2-high density lipoproteins were clearly identified by this method. In addition, our procedure was successfully applied to diagnosis of a patient with familial lecithin:cholesterol acyltransferase deficiency, characterized by the absence of alpha-high density lipoproteins.

Automation↗

Relationship between thyroid hormones and plasma D-dimer levels.

High serum levels of cholesterol and triglycerides are risk factors for coronary heart disease and are strongly related to several haemostatic parameters. Thyroid disorders are a frequent feature in hyperlipidemic patients and are also associated with a variety of haemostatic abnormalities. Therefore, we analysed the relationships between free T4 (fT4) levels and Factor VII and VIII activities (FVIIc and FVIIc), D-Dimers (DDI) and Plasminogen Activator Inhibitor type 1 (PAI-1), in a group of 472 healthy patients referred for hyperlipidemia. Fourty patients were found to have primary hypothyroidism. A negative correlation was found in the whole study population between fT4 and DDI (p = 0.0001, r = -0.21) and the same results were found after exclusion of the patients with fT4 below the normal range (p = 0.0007, r = -0.17). In a multivariate regression analysis, the relationship between DDI and fT4 was independent of age, Body Mass Index (BMI), gender and total cholesterol. Less impressive correlation coefficients were found with FVIIc (r = -0.10), FVIIIc (r = -0.09) and PAI-1 (r = -0.09). These results suggest that fT4 may play a physiological role in the regulation of the haemostatic equilibrium in hyperlipidemic patients and that low levels of fT4 are associated with a hypercoagulable state.

Adolescent↗

Direct isolation of labeled low density lipoproteins for the determination of cholesteryl ester transfer protein activity.

The measurement of the activity of cholesteryl ester transfer protein (CETP), is of high clinical interest and this study reports the use of a direct LDL isolation (d-LDL) technique to determine in one step the amount of radiolabeled cholesteryls esters ([3H]-CE) transferred from exogenous HDL3 to LDL, avoiding the conveniences of the usually used ultracentrifugation or precipitation of apo-B containing lipoproteins in the CETP methodologies. The d-LDL technique providing a specific immunoprecipitation of VLDL, IDL and HDL allowed to directly determine the [3H]-CE transferred on LDL (d-[3H]-CE-LDL). Two methodologies were assayed for the CETP activity using either exogenous or endogenous lipoproteins, and the results with the d-LDL technique were compared with those obtained using the ultracentrifugation (u-[3H]-CE-LDL) considered as the reference method. The intra- and inter-assays were similar in both techniques for the two CETP activity assays. Strong positive correlations were established between values obtained with d-[3H]-CE-LDL and u-[3H]-CE-LDL isolation procedures for CETP activities with exogenous or endogenous lipoproteins (r = 0.972; p = 0.0001 and r = 0.965; p = 0.0001 respectively). In conclusion, the d-LDL technique represents an easy and accurate procedure to measure directly, in normotriglyceridemic plasmas, the amount of [3H]-CE transferred from HDL to LDL by the CETP.

Carrier Proteins↗

The replacement of arginine by cysteine at residue 151 in apolipoprotein A-I produces a phenotype similar to that of apolipoprotein A-IMilano.

Rare nonsynonymous mutations in the apolipoprotein A-I (apo A-I) gene are associated with low HDL-cholesterol levels. Despite the inverse correlation of high density lipoprotein (HDL)-cholesterol levels with the risk of coronary heart disease (CHD) in the population, reduced circulating concentrations of HDL do not necessarily predispose to premature CHD. One apo A-I defect was even reported to cause longevity. We describe a French patient who presented with very low serum HDL-cholesterol levels (10 mg/dl). Sequence analysis of the apo A-I gene identified a heterozygous mutation in the apo A-I gene which causes a cysteine for arginine replacement at residue 151. Family members with the mutation displayed 50% lower levels of plasma HDL-cholesterol and of apo A-I than unaffected members. Plasma activity of lecithin:cholesterol acyl transferase (LCAT) was significantly lower in apo A-I(R151C) heterozygotes than in controls. Furthermore, we found that as for apo A-IMilano (R173C), apo A-I(R151C) forms heterodimers with apo A-II. Moreover, HDL particles were abnormal in both lipid composition and size distribution. Despite these quantitative and qualitative differences in HDL, neither the history of the family over three generations nor the examination of the patient, gave any indication of premature occurrence of atherosclerosis or CHD. We conclude that apo A-I(R151C) causes a phenocopy of apo A-IMilano (R173C), an apo A-I variant which is assumed to cause longevity and which is considered as a potentially anti-atherogenic agent.

Adult↗

Compound heterozygote for both rare apolipoprotein E1 (Gly127-->Asp, Arg158-->Cys) and E3(Cys112-->Arg, Arg251-->Gly) alleles in a multigeneration pedigree with hyperlipoproteinaemia.

1. A French multigeneration pedigree with hyperlipoproteinaemia was investigated for the transmission of the rare apolipoprotein E1(Gly127-->Asp, Arg158-->Cys) variant. The proband, a 46-year-old male carrying the rare apoE1 variant, presented a severe type III hyperlipoproteinaemia like his three brothers and his sister. 2. ApoE phenotyping and genotyping showed a discrepancy in the second allele carried by the proband's wife and two of her children, thus suggesting another apoE gene mutation. Cloning and sequencing of the entire exon 4 demonstrated a point mutation at codon 251, leading to an apoE3(Cys112-->Arg, Arg251-->Gly) allele. The proband's wife was normolipaemic and heterozygous for this rare isoform and the common apoE3 protein. The rare apoE3(Cys112-->Arg, Arg251-->Gly) allele has been transmitted to her two daughters. The first, aged 19, was normolipaemic and heterozygous for this allele and the common apoE2 allele. The second, carrying both the rare isoforms apoE1(Gly127-->Asp, Arg158-->Cys) and apoE3(Cys112-->Arg, Arg251-->Gly), presented a hypertriglyceridaemia at the age of 10. 3. The exploration of apoE status associated with plasma lipid levels and lipoprotein profiles in this three-generation pedigree made it possible to describe a compound heterozygote for two mutated alleles, one mutation being located in the N-terminal domain of the apoE protein and the other arising in the C-terminal domain.

Adult↗

[Lipoprotein glomerulopathy: a new French case with recurrence on the transplant].

Lipoprotein glomerulopathy is defined by the presence of lipidic deposits in the capillary lumen giving them a dialted and microaneurysmal aspect and the presence of quantitative and/or qualitative alterations of plasma apolipoprotein E. We describe here the long-term follow-up of a young female patient who presented with corticoresistant nephrotic syndrome in 1979 and progressed to chronic renal failure requiring dialysis in 1990. The three renal biopsies performed during the follow-up showed markedly enlarged capillary loops due to intra-luminal fibrinolipidic material deposition forming true intracapillary thrombi. She received a cadaver renal transplant in 1993. One year after transplantation, nephrotic syndrome reappeared and graft biopsy showed recurrence of the initial glomerular disease on the transplant. The plasma lipid profile showed hypercholesterolemia, hypertriglyceridemia, and elevated plasma ApoE levels with an abnormal Apo E phenotype. Our case report is a new typical case of lipoprotein glomerulopathy with recurrence of the initial disease on the renal allograft.

Adult↗