Icteric human samples: Icterus index and method of estimating an interference-free value for 16 biochemical analyses.

BACKGROUND: Hemolysis, Icterus, and Lipemia constituting the HIL index, are the most common causes of interference with accurate measurement in biochemistry. This study focuses on bilirubin interference, aiming to identify the analyses impacted and proposing a way to predict nominal interference-free analyte concentrations, based on both analyte level and Icterus Index (Iict ). METHODS: Sixteen common analytes were studied: alanine aminotransferase (ALT), albumin (ALB), alkaline phosphatase (ALP), amylase (AMY), aspartate aminotransferase (AST), total cholesterol (CHOLT), creatinine (CREA, enzymatic method), fructosamine (FRUC), gamma-glutamyl transferase (GGT), HDL cholesterol (HDLc), total iron (Iron), lipase (LIP), inorganic phosphorus (Phos), total protein (PROT), triglycerides (TG), and uric acid (UA). Both the traditional 10% change in concentrations from baseline and the Total Change Level (TCL) were taken as acceptance limits. Nineteen pools of sera covering a wide range of values were tested on the Cobas® 6000 (Roche Diagnostics). Iict ranged from 0 to 60. RESULTS: Eight analytes increased (FRUC and Phos) or decreased (CHOLT, CREA, HDLc, PROT, TG, and UA) significantly when Iict increased. FRUC, HDLc, PROT, and UA showed a linear relationship when Iict increased. A non-linear relationship was found for TG, CREA, and for CHOLT; this also depended on analyte levels. Others were not impacted, even at high Iict . CONCLUSIONS: A method of estimating an interference-free value for FRUC, HDLc, PROT, Phos, UA, TG, and CREA, and for CHOLT in cases of cholestasis, is proposed. Iict levels are identified based on analytical performance goals, and equations to recalculate interference-free values are also proposed.

A Combination of Single-Nucleotide Polymorphisms Is Associated with Interindividual Variability in Cholecalciferol Bioavailability in Healthy Men.

BACKGROUND: Most people require dietary vitamin D to achieve the recommended concentration of 25-hydroxyvitamin D [25(OH)D] in the blood. However, the response to vitamin D supplementation is highly variable among individuals. OBJECTIVE: We assessed whether the variability in cholecalciferol bioavailability was associated with single-nucleotide polymorphisms (SNPs) in candidate genes. METHODS: In a single-group design, 39 healthy adult men with a mean ± SD age of 33 ± 2 y and mean ± SD body mass index (in kg/m2) of 22.9 ± 0.3 were genotyped with the use of whole-genome microarrays. After an overnight fast, plasma 25(OH)D status was measured, and the subjects then consumed a meal that provided 5 mg cholecalciferol as a supplement. Plasma chylomicron cholecalciferol concentration was measured over 8 h, and cholecalciferol response was assessed by calculating the postprandial area under the curve. Partial least squares regression was used to test the association of SNPs in or near candidate genes (61 genes representing 3791 SNPs) with the postprandial cholecalciferol response. RESULTS: The postprandial chylomicron cholecalciferol concentration peaked at 5.4 h. The cholecalciferol response was extremely variable among individuals (CV: 47%). It correlated with the chylomicron triglyceride (TG) response (r = 0.60; P < 0.001) but not with the fasting plasma 25(OH)D concentration (r = 0.04; P = 0.83). A significant (P = 1.32 × 10-4) partial least squares regression model that included 17 SNPs in 13 genes (including 5 that have been associated with chylomicron TG response) was associated with the variance in the cholecalciferol response. CONCLUSION: In healthy men, there is a high interindividual variability in cholecalciferol bioavailability that is associated with a combination of SNPs located in or near genes involved in both vitamin D and lipid metabolism. This trial was registered at clinicaltrials.gov as NCT02100774.

Growth hormone level at admission and its evolution during refeeding are predictive of short-term outcome in restrictive anorexia nervosa.

The growth hormone (GH)­insulin-like growth factor-1 (IGF-1) axis is dramatically altered in patients with anorexia nervosa (AN). The aim of the present study was to investigate whether GH and IGF-1 could be predictors of outcome in patients with a restrictive form of AN. Blood levels of GH, IGF-1, adipocytokines, ghrelin, insulin, glucose, and sex and thyroid hormones were measured in eleven women inpatients with AN and in ten healthy women controls. Three stages were compared during refeeding: admission (T0), when BMI reached 16 kg/m2 (T1) and at discharge when BMI reached 17.5 kg/m2 (T2). Clinical status was assessed 6 months after discharge from hospital (T3), and remission was defined by the maintenance of a BMI > or = 17.5 kg/m2. AN patients in remission (AN-R; n 6) had significantly higher GH levels at admission than those who relapsed (AN-NR; n 5) (P < 0.05). During refeeding (delta = T2 - T0), the AN-R group differed from the AN-NR group only by both GH level decrease (P < 0.05) and BMI increase (P < 0.05). In multiple regression analysis, delta GH was associated negatively and significantly and delta leptin and delta body fat mass levels were associated positively and significantly with BMI at T3 and explained 88% of its variability (r2 0.88, P < 0.05). The present study suggests that a low GH level at admission and the absence of its decrease after weight recovery could predict short-term relapse in women suffering from a restrictive form of AN.

Cholesterol-absorber status modifies the LDL cholesterol-lowering effect of a Mediterranean-type diet in adults with moderate cardiovascular risk factors.

LDL-cholesterol (LDL-C) reduction may be achieved by various types of prudent diets, but their effects on surrogate markers of cholesterol absorption and synthesis have not been well studied in humans. We aimed to assess whether the extent of cholesterol absorption or synthesis, and cholesterol concentrations, are modified in adults when they shift from a Western-type diet (WD) to a combined low-fat, low-cholesterol/Mediterranean-type diet (LFCMD). Cholestanol and sitosterol, as well as desmosterol and lathosterol, surrogate markers of cholesterol absorption or synthesis, respectively, were quantified in the serum of 125 fasting, middle-aged participants at moderate cardiovascular risk. They habitually consumed a WD and then consumed a LFCMD during the 3-mo intervention. The group was stratified by serum cholestanol concentration and classified as high, intermediate, or low absorbers of cholesterol. When they consumed the WD, participants had comparable total and LDL-C concentrations, independent of absorber group and sex. After 3 mo of consuming the LFCMD, absorption and synthesis did not change or changed only slightly. The cholestanol concentration increased in low absorbers by 18% (P < 0.02) and decreased in high absorbers by 14% (P < 0.001), but these variations did not change the high- or low-absorber status. In male and female low absorbers, plasma total (-7%) and LDL-C (-9%) concentrations decreased after the 3-mo intervention and changes were 2.3- and 2.4-fold greater, respectively, than in high absorbers, independent of sex. Cholesterol synthesis/absorption status was not markedly altered by diet, but the decrease in plasma LDL-C due to the Mediterranean-type diet occurred only in low absorbers of cholesterol. This should be considered during further dietary interventions.

Recommendations for the application and follow-up of quality controls in medical laboratories.

This is a translation of the paper "Recommendations for the application and follow-up of quality controls in medical biology laboratories" published in French in the journal Annales de Biologie Clinique (Recommandations pour la mise en place et le suivi des contrôles de qualité dans les laboratoires de biologie médicale. Ann Biol Clin (Paris). 2019;77:577-97.). The recommendations proposed in this document are the result of work conducted jointly by the Network of Accredited Medical Laboratories (LABAC), the French Society of Medical Biology (SFBC) and the Federation of Associations for External Quality Assessment (FAEEQ). The different steps of the implementation of quality controls, based on a risk analysis, are described. The changes of reagent or internal quality control (IQC) materials batches, the action to be taken in case of non-conform IQC results, the choice of external quality assessment (EQA) scheme and interpretation of their results as well as the new issue of analyses performed on several automatic systems available in the same laboratory are discussed. Finally, the concept of measurement uncertainty, the robustness of the methods as well as the specificities of near-patient testing and rapid tests are described. These recommendations cannot apply for all cases we can find in medical laboratories. The implementation of an objective alternative strategy, supported with documented evidence, might be equally considered.

Plasma adiponectin in heart transplant recipients.

BACKGROUND: The association between plasma adiponectin and metabolic syndrome may be impaired in heart transplant recipients, since renal failure is frequent among these patients. Thus, we studied the relationship between metabolic syndrome and plasma adiponectin in transplanted heart recipients. METHODS: Ninety-five heart transplant recipients were prospectively included 8.3 +/- 5.6 yr after transplantation in this cross-sectional study. All patients had physical examination, echocardiography or routine biennial coronary angiography, and laboratory measurements. RESULTS: Metabolic syndrome was found in 31% of these patients. Plasma adiponectin was significantly lower in patients with metabolic syndrome (12.5 +/- 8.3 microg/mL) than in patients without (16.7 +/- 9.4 microg/mL, p = 0.03). Adiponectin levels were usually in the normal or high range (< 4 microg/mL in only two patients). Low creatinine clearance was associated with higher plasma adiponectin (R=-0.26, p = 0.01). Plasma adiponectin was not significantly different between the 28 patients with angiographic evidence of graft vasculopathy (13.9 +/- 9.5 microg/mL) and the 67 patients without (16.1 +/- 9.1 microg/mL, p = 0.3). CONCLUSIONS: Contrasting with a high frequency of metabolic syndrome in these patients, adiponectin levels were usually in the normal or high range, probably as a consequence of renal failure. This suggests that adiponectin is not a major determinant for insulin resistance among these patients.

Human fasting plasma concentrations of vitamin E and carotenoids, and their association with genetic variants in apo C-III, cholesteryl ester transfer protein, hepatic lipase, intestinal fatty acid binding protein and microsomal triacylglycerol transfer protein.

Plasma concentrations of vitamin E and carotenoids are governed by several factors, including genetic factors. Single nucleotide polymorphisms (SNP) in some genes involved in lipid metabolism have recently been associated with fasting plasma concentrations of these fat-soluble micronutrients. To further investigate the role of genetic factors that modulate the plasma concentrations of these micronutrients, we assessed whether SNP in five candidate genes (apo C-III, CETP, hepatic lipase, I-FABP and MTP) were associated with the plasma concentrations of these micronutrients. Fasting plasma vitamin E and carotenoid concentrations were measured in 129 French Caucasian subjects (forty-eight males and eighty-one females). Candidate SNP were genotyped by PCR amplification followed by restriction fragment length polymorphisms. Plasma gamma-tocopherol, alpha-carotene and beta-carotene concentrations were significantly different (P < 0.05) in subjects who carried different SNP variants in hepatic lipase. Plasma alpha-tocopherol concentrations were significantly different in subjects who had different SNP variants in apo C-III and cholesteryl ester transfer protein (CETP). Plasma lycopene concentrations were significantly different (P < 0.05) in women who had different SNP variants in intestinal fatty acid binding protein (I-FABP). Finally, there was no effect of SNP variants in microsomal TAG transfer protein upon the plasma concentrations of these micronutrients. Most of the observed differences remained significant after the plasma micronutrients were adjusted for plasma TAG and cholesterol. These results suggest that apo C-III, CETP and hepatic lipase play a role in determining the plasma concentrations of tocopherols while hepatic lipase and I-FABP may modulate plasma concentrations of carotenoids.

The effect of apoE genotype and sex on ApoE plasma concentration is determined by dietary fat in healthy subjects.

The interindividual variation in ApoE plasma concentration is considerable, mainly determined by apoE genotype and sex. However, a large amount of variability remains unexplained by these factors. We have evaluated whether the quantity and quality of dietary fat interacts with the apoE genotype and sex modifying ApoE plasma levels in young healthy subjects. Eighty-four volunteers (sixty-six apoE3/3, eight apoE4/3 and ten apoE3/2) were subjected to three dietary periods, each lasting 4 weeks. The first was a SFA-enriched diet (38 % fat and 20 % SFA), which was followed by a carbohydrate (CHO)-rich diet (30 % fat, < 10 % SFA and 55 % carbohydrate) or a MUFA-rich diet (38 % fat and 22 % MUFA) following a randomised crossover design. apoE2 carriers have the highest ApoE levels, whereas apoE4 individuals show the lowest concentration after the SFA, CHO and MUFA diets. Women had significantly higher ApoE concentration than men only after the consumption of the SFA diet. The SFA diet increased the ApoE plasma concentration when compared with the CHO- and MUFA-rich diets in women, but not in men. In women, but not in men, the shift from the SFA- to CHO- or MUFA-rich diets significantly decreased the ApoE concentration in apoE3/2 and apoE3/3 subjects, whereas no differences were observed in women with the apoE4/3 genotype. Sex and apoE genotype determine ApoE plasma levels; however, this effect is dependent on dietary fat.

[Recommendations for the application and the follow-up of quality controls in medical biology laboratories]. / Recommandations pour la mise en place et le suivi des contrôles de qualité dans les laboratoires de biologie médicale.

The recommendations that we formulate in this document come from LABAC, SFBC and FAEEQ. They describe the different steps from the initial application of quality controls, based on risk analysis: the changes of reagent batches or internal quality controls (IQC) batches, the course when IQC are not in accordance with references, the choice of external quality evaluation and the interpretation of its results, the comparability of results obtained in several analysers used in the same laboratory. Lastly, measurement uncertainty, robustness of methods and specificities of near-patient biology and rapid tests are described. Note that these recommendations cannot develop all cases that we could find in laboratories. It remains necessary to carry out an objective strategy, supported with documentary evidences.

Pharmacodynamics of unfractionated heparin during and after a hemodialysis session.

BACKGROUND: Anti-Xa activity is used as a clinical guide to anticoagulation with heparin, but heparin dosing regimens for hemodialysis were established before anti-Xa assays were developed; thus, the optimal regimen for heparin dosing was not determined. The aim is to confirm the interesting characteristics of unfractionated heparin pharmacokinetics for hemodialysis anticoagulation, provide insight into the hemorrhagic risk of hemodialysis patients, and determine the dose of unfractionated heparin and its adequate mode of administration. STUDY DESIGN: Cross-sectional study of the pharmacokinetics of unfractionated heparin performed during and after a 4-hour midweek hemodialysis session. SETTING & PARTICIPANTS: 35 long-term hemodialysis patients at the Sainte-Marguerite Unit of the Marseille University Hospital, Marseille, France. PREDICTOR: Hemodialysis anticoagulation with continuous unfractionated heparin infusion at a dose of 50 IU/kg/session (25 IU/kg/h during the first hour, 12.5 IU/kg during the second and third hours, and stop during the last hour). OUTCOME & MEASUREMENTS: Anti-Xa activity was monitored during the 10 hours after the beginning of the hemodialysis session. Levels of 0.3 to 0.7 IU/mL are considered sufficient for anticoagulation. Pharmacokinetics was determined by using a population approach (nonlinear mixed-effects modeling). The final model and corresponding parameter values (including interindividual and residual variability) were used to simulate 1,000 replicates. RESULTS: No case of clotting was recorded. A pharmacokinetic model with 1 compartment and first-order elimination best fitted the data. Terminal half-life was 54 minutes. Median anti-Xa activities were 0.55 IU/mL at peak, 0.25 IU/mL at end of the 4-hour session, and less than 0.1 IU/mL at 90 minutes after the session. We simulated a continuous infusion of the dose of 50 IU/kg for 1, 2, 3, and 4 hours. Peak values were 1.1, 0.8, 0.6, and 0.5 IU/mL, respectively. Values at the end of the session were 0.12, 0.18, 0.3, and 0.5 IU/mL, respectively. Values became less than 0.1 IU/mL at 15, 60, 105, and 120 minutes after the session, respectively. LIMITATIONS: Interindividual variability in unfractionated heparin pharmacokinetics. CONCLUSIONS: Unfractionated heparin administered by means of a 3-hour continuous infusion for hemodialysis anticoagulation provided an efficient and safe effect that quickly disappeared after the end of the session.

Sex-specific association of fatty acid binding protein 2 and microsomal triacylglycerol transfer protein variants with response to dietary lipid changes in the 3-mo Medi-RIVAGE primary intervention study.

BACKGROUND: The dietary guidelines targeted at reducing cardiovascular risk lead to largely heterogeneous responses in which genetic determinants are largely involved. OBJECTIVES: We evaluated the effect of fatty acid binding protein 2 (FABP2) Ala54Thr and microsomal triacylglycerol transfer protein (MTTP) -493G/T allelic variations on plasma lipid markers, at baseline and on the response to the 3-mo Medi-RIVAGE primary prevention study. DESIGN: Subjects with moderate cardiovascular disease risk (n = 169) were advised to reduce total and saturated dietary fats and to increase intake of monounsaturated and polyunsaturated fats. They were genotyped for FABP2 Ala54Thr and MTTP -493G/T allelic variations, and plasma was processed for cardiovascular risk marker analyses. RESULTS: At baseline, men and women homozygous for Thr54 presented a significant opposite profile for plasma oleic acid (18:1), triacylglycerol-rich lipoprotein (TRL) cholesterol, and TRL phospholipids. In addition, all Thr/Thr men presented higher 18:1 values than did women. For the MTTP -493G/T polymorphism, although all TT subjects presented high apolipoprotein B-48, a genotype x sex interaction was present for palmitic acid, linolenic acid, eicosatrienoic acid, and insulin. The prudent diet clearly improved plasma lipid markers. FABP2 genotype did not interact much with the amplitude of the response. However, for MTTP polymorphism, men homozygous for the T allele displayed a significantly more pronounced response than did men carrying the G allele, which is particularly evident by their larger decrease in the Framingham score. CONCLUSIONS: These 2 polymorphic loci are thus differently associated with the baseline lipid markers as well as with the response to nutritional recommendations, but both presented a marked sex-specific profile, with the response to diet being particularly efficient in men homozygous for the MTTP -493T allele.

Human plasma levels of vitamin E and carotenoids are associated with genetic polymorphisms in genes involved in lipid metabolism.

Vitamin E and carotenoids are fat-soluble micronutrients carried by plasma lipoproteins. Their plasma concentrations are governed by several factors, some of which are genetic, but data on these genetic factors remain scarce. We hypothesized that genes involved in lipid metabolism, i.e. the genes implicated in intestinal uptake, intracellular trafficking, and the lipoprotein distribution of lipids, play a role in the plasma concentrations of these micronutrients. To verify this hypothesis, we assessed whether the plasma status of vitamin E and carotenoids is related to genes involved in lipid metabolism. Fasting plasma vitamin E (alpha- and gamma-tocopherol) and carotenoid (alpha- and beta-carotene, lutein, lycopene, beta-cryptoxanthin, and zeaxanthin) concentrations were measured in 48 males and 80 females. The following genes were genotyped [single nucleotide polymorphisms (SNP)]: apolipoprotein (apo) A-IV, apo B, apo E, lipoprotein lipase, and scavenger-receptor class B type I (SR-BI). Plasma alpha-tocopherol concentrations were different (P < 0.05) in subjects bearing different SNP in apo A-IV, apo E, and SR-BI. Plasma gamma-tocopherol concentrations were different (P < 0.05) in subjects bearing different SNP in apo A-IV and SR-BI. Alpha-carotene concentrations were different (P < 0.05) in subjects bearing different SNP in SR-BI. Beta-carotene concentrations were different (P < 0.05) in subjects bearing different SNP in apo B and SR-BI. Lycopene concentrations were different (P < 0.05) in subjects bearing different SNP in apo A-IV and apo B. Beta-cryptoxanthin concentrations were different (P < 0.05) in subjects bearing different SNP in SR-BI. Plasma lutein and zeaxanthin concentrations did not differ in subjects bearing different SNP. Most of the differences remained significant after the plasma micronutrients were adjusted for plasma triglycerides and cholesterol. These results suggest that genes involved in lipid metabolism influence the plasma concentrations of these fat-soluble micronutrients.

Evaluation of new apolipoprotein C-II and apolipoprotein C-III automatized immunoturbidimetric kits.

BACKGROUND: Apolipoprotein C-II and apolipoprotein C-III play an important and complex role in plasma triglycerides metabolism, respectively, as inhibitor and activator of lipoprotein lipase. Thus, they appear to be suitable markers for clinical studies of triglyceride-rich lipoproteins and related cardiovascular risk. Our aim was to evaluate, for routine analysis, the accuracy to quantify these apolipoprotein in human sera. METHODS: Precision (intra- and inter-run), limit of detection and quantification, linearity, common interferents (lipids, haemoglobin, bilirubin) and reference intervals were determined according to guidelines of the French Society of Clinical Biology and ISO Norm 5725 specifications. RESULTS: Intra- and inter-run CVs were respectively less than 5.0% and 7.5%. Linearities extended from 10.8 mg/L to 112.9 mg/L for apolipoprotein C-II and from 31.8 mg/L to 375.5 mg/L for apolipoprotein C-III. Haemolysis (up to 227.6 micromol/L haemoglobin) and lipemia (up to 19.3 mmol/L triglycerides) do not interfere, contrary to bilirubin, which has a positive effect above 350 micromol/L. Comparison of methods shows good agreement between immunoturbidimetric and electro-immunodiffusion methods for measuring apolipoprotein C-III in 62 samples within a wide range (n = 62, r = 0.954, y = 3.81 x -14.4). CONCLUSION: This study shows the reliability of these kits for measuring apolipoprotein C-II and apolipoprotein C-III in human sera, and their suitability for routine analysis.

Concomitant cell growth and differentiation are dependent on erbB1 and integrin activation in an autonomously surviving colon adenocarcinoma: involvement of autocrine amphiregulin secretion.

In normal colon epithelium, cell proliferation is followed by cell differentiation. The purpose of this work was to investigate, in the HT29-D4 colon adenocarcinoma cell line, the occurrence of a temporal sequence of changes in cell proliferation and differentiation, the role of autocrine EGF family ligands and to determine which transduction pathway(s) are involved in these processes. In a medium lacking both growth factor and serum, HT29-D4 cells secreted amphiregulin (AR), which was shown to be strongly involved in cell adhesion, growth and differentiation. In the main, integrins alpha2beta1 and alphavbeta6 intervened in these processes. Using tyrphostins, it was demonstrated that AR involvement was mediated through the ErbB1/ERK1,2 and ErbB1/FAK pathways. These signalling molecules were directly involved in pRb inhibition and, thus, in cyclin A expression. Concomitantly, colon differentiation markers were also expressed. Furthermore, terminal cell maturation resulted in a colon absorptive cell with strong polarisation, the growth of which was inhibited by tyrphostin and an ERK1,2 inhibitor. It was concluded that in a colon adenocarcinoma, cell proliferation and differentiation can occur concomitantly and that these deregulated processes are controlled by autocrine secretion through the ErbB1/ERK1,2 and FAK pathways.

Lutein transport by Caco-2 TC-7 cells occurs partly by a facilitated process involving the scavenger receptor class B type I (SR-BI).

The carotenoid lutein is thought to play a role in the human eye and to protect against age-related macular degeneration. Lutein transport in the human intestine has not been characterized. We examined lutein transport processes using Caco-2 TC-7 monolayers as a model for human intestinal epithelium. Purified lutein was mixed with phospholipids, lysophospholipids, cholesterol, mono-olein, oleic acid and taurocholate to obtain lutein-rich mixed micelles that mimicked those found under physiological conditions. The micelles were added to the apical side of Caco-2 TC-7 cell monolayers for 30 min or 3 h at 37 degrees C. Absorbed lutein, i.e. the sum of lutein recovered in the scraped cells and in the basolateral chamber, was quantified by HPLC. Transport rate was measured (i) as a function of time (from 15 to 60 min), (ii) as a function of micellar lutein concentration (from 1.5 to 15 microM), (iii) at 4 degrees C, (iv) in the basolateral to apical direction, (v) after trypsin pretreatment, (vi) in the presence of beta-carotene and/or lycopene, (vii) in the presence of increasing concentrations of antibody against SR-BI (scavenger receptor class B type 1) and (viii) in the presence of increasing concentrations of a chemical inhibitor of the selective transfer of lipids mediated by SR-BI, i.e. BLT1 (blocks lipid transport 1). The rate of transport of lutein as a function of time and as a function of concentration was saturable. It was significantly lower at 4 degrees C than at 37 degrees C (approx. 50%), in the basal to apical direction than in the opposite direction (approx. 85%), and after trypsin pretreatment (up to 45%). Co-incubation with beta-carotene, but not lycopene, decreased the lutein absorption rate (approx. 20%) significantly. Anti-SR-BI antibody and BLT1 significantly impaired the absorption rate (approx. 30% and 57% respectively). Overall, these results indicate that lutein absorption is, at least partly, protein-mediated and that some lutein is taken up through SR-BI.

A chronicle of the changes undergone by a maritime territory, the Bay of Toulon (Var Coast, France), and their consequences on PCB contamination.

This study evaluated the distribution of polychlorinated biphenyls (PCBs) in 39 surface sediment samples and four cores collected in Toulon Bay, a semiclosed area submitted to various anthropogenic inputs. The concentration of PCBs in the superficial sediment samples ranged from 1.7 to 2530 ng g(-1) dry weight. The spatial distribution of these compounds suggested that the high concentrations of these contaminants are located in the small bay and are related to human activities. In the larger bay, the concentrations were in the same order of magnitude than those reported in others locations around the world. Comparison of the levels with target values from the French legislation shows that, except for four polluted sites with critical values (N2: values ≥1 mg kg(-1) dry weight) in the smaller bay, PCBs levels throughout the larger and the smaller bay are lower than the accepted values (N1: values <0.5 mg kg(-1) dry weight). The PCBs in the sediment cores ranged from 0.8 to 739 ng g(-1) dry weight dependent core. Vertical profiles indicated earlier usage of PCBs which coincided with the history of the Toulon Bay. In this study, using alkane, we could follow the PCBs pollution history over about 80 years and estimate a sedimentation rate of about 0.32 cm year in the small Bay of Toulon.

The Medi-RIVAGE study: reduction of cardiovascular disease risk factors after a 3-mo intervention with a Mediterranean-type diet or a low-fat diet.

BACKGROUND: Epidemiologic studies link Mediterranean-type diets to a low incidence of cardiovascular disease; however, few dietary intervention studies have been undertaken, especially in primary prevention. OBJECTIVES: In the Mediterranean Diet, Cardiovascular Risks and Gene Polymorphisms (Medi-RIVAGE) study, the effects of a Mediterranean-type diet (Med group) or a low-fat diet (low-fat group) on risk factors were evaluated in 212 volunteers (men and women) with moderate risk factors for cardiovascular disease. DESIGN: After the 3-mo dietary intervention, changes in many risk factors were evaluated. Dietary questionnaires and plasma nutritional markers were used to test compliance. RESULTS: Although the dietary goals were only partially reached, changes in dietary habits were observed in both groups (n = 169): protein, carbohydrate, and fiber intakes increased and fat quality (decreased saturated fat and increased monounsaturated or polyunsaturated fat) improved. BMI, total and triacylglycerol-rich lipoprotein (TRL) cholesterol, triacylglycerols, TRL triacylglycerols, apolipoproteins A-I and B, insulinemia, glycemia, and the homeostasis model assessment score were significantly lower after 3 mo. The reductions in total cholesterol, triacylglycerols, and insulinemia remained significant after adjustment for BMI. There was a trend for a diet-by-time interaction for LDL cholesterol (P = 0.09). Our data predicted a 9% reduction in cardiovascular disease risk with the low-fat diet and a 15% reduction with this particular Mediterranean diet. CONCLUSION: After a 3-mo intervention, both diets significantly reduced cardiovascular disease risk factors to an overall comparable extent.

Fasting apoprotein B-48 level and coronary artery disease in a population without frank fasting hypertriglyceridemia.

The aim of this study was to test the hypothesis that fasting apoprotein B-48 level might be a surrogate marker of postprandial lipemia in evaluating the risk of coronary artery disease (CAD) in a population without frank abnormality in fasting lipid profile. One hundred twenty-three patients tested by coronary angiography were selected on the criteria of absence of treatment with hypolipidemic drugs, obvious hypertriglyceridemia (>2.85 mmol/L), or other conditions that may interfere with lipoprotein metabolism except diabetes. CAD was defined by more than 50% narrowing of vessel lumen, and its severity is determined by the number of arteries involved. Fasting apoprotein B-48 was measured by a competitive enzyme-linked immunosorbent assay method. There was no difference in fasting apoprotein B-48 levels between the groups with and without CAD (0.123+/-0.096 vs 0.136+/-0.125 microg/mL, respectively), whatever the sex or whether with or without diabetes. The apoprotein B-48 level was not related to the presence or the severity of CAD. There was also no correlation between fasting apoprotein B-48 levels and age, sex, body mass index, and usual fasting lipid parameters in both patients with and without angiographically proven CAD. Finally, among the features of metabolic syndrome, apoprotein B-48 was correlated with fasting triglyceride levels (r=0.357, P<.01) only. In conclusion, the present study shows that in the absence of any major fasting abnormality in plasma lipid parameters, fasting apoprotein B-48 level, which has been associated with postprandial hyperlipidemia, does not predict the risk of CAD.

High-fat diets impede the lowering effect of cyclosporine A on rat brain lipids and interact with the expression of apolipoproteins E and J.

Cyclosporine A (CsA), a common immunosuppressive agent, produces hyperlipidemia and apolipoprotein profile alterations in plasma as well as neurological and psychiatric complications. In rats, 10 mg CsA/kg/d treatments for 3 wk induce alterations of the electroencephalogram, and of the blood and brain lipids. Using this model, we evaluated whether triacylglycerol (TG)- and lecithin (PC)-enriched diets, reported to decrease epileptic episodes (TG) and to improve memory, could modify the effects of CsA treatment on brain lipids and possibly change apolipoprotein (apo) E and apoJ gene expression. To evaluate this hypothesis, three groups of rats were treated for 3 wk with CsA and received a low-fat, PC, or TG diet. Three other groups were fed the above-mentioned diets and were treated with the CsA solvent. As a control, one group was fed only the low-fat diet. The CsA-mediated decreases in brain cholesterol and PC contents, under a low-fat diet, were eliminated by the TG and PC diets. These high-fat diets induced a global increase in hippocampal transcriptional activity, as revealed by elevated polyadenylated RNA levels. The apoE and apoJ mRNA levels in the cortex and hippocampus of rats receiving the solvent were not statistically different between the TG- and PC-enriched diets but showed important variations compared with the low-fat diet solvent-treated group. A differential effect between the two high-fat diets was observed in the hippocampus, resulting in a significant increase of the apoE to apoJ ratio with the PC diet. The balance between apoE and apoJ is presumed to be important in encephalopathic mechanisms, by its involvement through low levels of brain cholesterol and PC, that might be associated with mental disorders. Our results therefore suggest that diet enrichment with polyunsaturated fat might be beneficial during CsA therapy. However, if the high levels in PC used here are more beneficial on CsA peripheral side effects than similar enrichment in TG, this does not seem to be the case in the brain. Thus, lower levels in PC should be tested.

The Transcriptional Effects of PCB118 and PCB153 on the Liver, Adipose Tissue, Muscle and Colon of Mice: Highlighting of Glut4 and Lipin1 as Main Target Genes for PCB Induced Metabolic Disorders.

Epidemiological studies have associated environmental exposure to polychlorinated biphenyls (PCBs) with an increased risk of type 2 diabetes; however, little is known about the underlying mechanisms involved in the metabolic side-effects of PCB. Our study evaluated the transcriptional effects of a subchronic exposure (gavage at Day 0 and Day 15 with 10 or 100 µmol/Kg bw) to PCB118 (dioxin-like PCB), PCB153 (non-dioxin-like PCB), or an equimolar mixture of PCB118 and PCB153 on various tissues (liver, visceral adipose tissue, muscle, and colon) in mice. Our results showed that a short-term exposure to PCB118 and/or PCB153 enhanced circulating triglyceride levels but did not affect glycemia. Among the studied tissues, we did not observe any modification of the expression of inflammation-related genes, such as cytokines or chemokines. The main transcriptional effects were observed in visceral adipose and liver tissues. We found a downregulation of lipin1 and glut4 expression in these two target organs. In adipose tissue, we also showed a downregulation of Agpat2, Slc25a1, and Fasn. All of these genes are involved in lipid metabolism and insulin resistance. In muscles, we observed an induction of CnR1 and Foxo3 expression, which may be partly involved in PCB metabolic effects. In summary, our results suggest that lipin1 and glut4, notably in adipose tissue, are the main targeted genes in PCB-induced metabolic disorders, however, further studies are required to fully elucidate the mechanisms involved.