[Evaluation of the efficacy and safety of HIVEC intravesical thermochemotherapy with intermediate-risk and high-risk non-muscle-invasive bladder cancer]. / Évaluation de l'efficacité et de la tolérance de la thermo-chimiothérapie intravésicale HIVEC pour les tumeurs de vessie non infiltrant la musculeuse de risque intermédiaire et de haut risque.

INTRODUCTION: Non-muscle-infiltrating cancers (NMIBC) represent 75% of bladder tumors. The objective of our study is to report a single-center experience of the efficacy and tolerability of HIVEC on intermediate- and high-risk NMIBC in adjuvant therapy. MATERIAL AND METHOD: Between December 2016 and October 2020, patients with intermediate-risk or high-risk NMIBC were included. They were all treated with HIVEC as an adjuvant therapy to bladder resection. Efficacy was assessed by endoscopic follow-up and tolerance by a standardized questionnaire. RESULTS: A total of 50 patients were included. The median age was 70years (34-88). The median follow-up time was 31 months (4-48). Forty-nine patients had cystoscopy as part of the follow-up. Nine recurred. One patient progressed to Cis. The 24-month recurrence-free survival was 86.6%. There were no severe adverse events (grade 3 or 4). The ratio of delivered instillations to planned instillations was 93%. CONCLUSION: HIVEC with the COMBAT system is well tolerated in adjuvant treatment. However, it is not better than standard treatments, especially for intermediate-risk NMIBC. While waiting for recommendations, it cannot be proposed as an alternative to standard treatment.

Engineering of III-Nitride Semiconductors on Low Temperature Co-fired Ceramics.

This work presents results in the field of advanced substrate solutions in order to achieve high crystalline quality group-III nitrides based heterostructures for high frequency and power devices or for sensor applications. With that objective, Low Temperature Co-fired Ceramics has been used, as a non-crystalline substrate. Structures like these have never been developed before, and for economic reasons will represent a groundbreaking material in these fields of Electronic. In this sense, the report presents the characterization through various techniques of three series of specimens where GaN was deposited on this ceramic composite, using different buffer layers, and a singular metal-organic chemical vapor deposition related technique for low temperature deposition. Other single crystalline ceramic-based templates were also utilized as substrate materials, for comparison purposes.

The nanostructure of porous cobalt coatings deposited by magnetron sputtering in helium atmosphere.

In this work, (scanning) transmission electron microscopy has been used to study the nanostructure of porous cobalt coatings obtained by magnetron sputtering using helium as process gas. This nanostructure consists of closed pores of different nanometric size (about 4-20 nm) that are distributed all over a nanocrystalline Co matrix and filled with the deposition gas. Spatially resolved electron energy-loss spectroscopy analysis was applied to measure and map, with high lateral resolution, the relevant physical properties (density, pressure and He-K edge shift) of helium trapped inside these individual nanopores, in order to provide new insights about the growth mechanism involved in such systems. In particular, a coefficient of proportionality, C = 0.039 eV nm3, between the blue shift of the He K-edge and the He density has been found. In addition, very high He densities (10-100 at./nm3) and pressures in the gigapascal range (0.05-5.0 GPa) have been measured. The linear dependence of these parameters as a function of the inverse radii obeying to the Laplace-Young law for most of the pores suggests that their formation during the coating's growth takes place in regime of elastic deformation of the Co matrix.

Simultaneous Exposure-Response Modeling of ACR20, ACR50, and ACR70 Improvement Scores in Rheumatoid Arthritis Patients Treated With Certolizumab Pegol.

The Markovian approach has been proposed to model American College of Rheumatology's (ACR) response (ACR20, ACR50, or ACR70) reported in rheumatoid arthritis clinical trials to account for the dependency of the scores over time. However, dichotomizing the composite ACR assessment discards much information. Here, we propose a new approach for modeling together the three thresholds: a continuous-time Markov exposure-response model was developed, based on data from five placebo-controlled certolizumab pegol clinical trials. This approach allows adequate prediction of individual ACR20/50/70 time-response, even for non-periodic observations. An exposure-response was established over a large range of licensed and unlicensed doses including phase II dose-ranging data. Simulations from the model (50-400 mg every other week) illustrated the range and sustainability of response (ACR20: 56-68%, ACR50: 27-42%, ACR70: 11-22% at week 24) with maximum clinical effect achieved at the recommended maintenance dose of 200 mg every other week.

[Preoperative endorectal MRI in prostate cancer: a monocentric retrospective cohort]. / Place de l'IRM prostatique avant prostatectomie radicale. Cohorte monocentrique rétrospective.

INTRODUCTION: The aim of the study was to assess the added value of a prostatic MRI performed in a non-expert center before radical prostatectomy for prostate cancer. PATIENTS AND METHODS: All patients considered for a radical prostatectomy for a clinically localised prostate cancer in our institution between June 2006 and April 2011 were analysed. They underwent a systematic endorectal 1.5 T MRI [eMRI] (T2 and diffusion-weighted imaging). The procedure was performed at least 8 weeks after transrectal ultrasound guided prostate biopsies. They were analyzed by a single experimented genitourinary radiologist. The preoperative characteristics and biopsy data were collected, as the eMRI interpretation using a systematic scale. Correlation between eMRI and final histopathology has been analyzed (standardized pathological report using the Stanford procedure). We considered the following points: extracapsular extension, seminal vesicle invasion and cancer localisation. Cancer localization was analyzed both by halves (left/right) and on sextant-basis (base, middle, apex, left and right respectively). For each data, sensitivity, specificity, positive (PPV) and negative predictive value (NPV) were calculated. Finally, we compared the results with those from the Partin's table and the Kattan's nomogram for T stage. RESULTS: Two hundred and fifteen patients underwent a radical prostatectomy, having a mean age of 63 ± 6 years, a mean PSA: 7.8 ± 3.8 ng/mL. One hundred and fifty-nine patients had organ confined disease. Fifty-six had pT3 disease (50 pT3a and 6 pT3b). Sensibilities and specificities were the following: for extracapsular extension 26% and 96%; for seminal vesicle invasion 17% and 98%; for cancer localisation 64% and 74%; for prediction of left or right side 81% and 48%. DISCUSSION: MRI showed equal performances compared to the Partin's table and the Kattan's nomogram for T stage. It showed lower performance compared to biopsy results for cancer localization (sensitivity 88%, specificity 70%). Literature provides wide ranges of results for eMRI. The results of this study were at the low limit of these ranges but reflect everyday practice. When performed, as it was in our study, eMRI did not seem to be accurate for staging. It had at best a very limited added value compared to the existing tools.

[Prone and supine position for percutaneous nephrolithotomy: is it necessary to change the operative technique?]. / Néphrolithotomie percutanée : faut-il passer du décubitus ventral au décubitus dorsal ?

PURPOSE: To assess the safety and effectiveness of percutaneous nephrolithotomy performed in the supine position. To investigate whether the change in operative technique, between prone and supine position, is easy. METHOD: Thirty patients who underwent percutaneous nephrolithotomy, by one surgeon in one hospital, were studied retrospectively. The eight first cases were performed in prone position, and the following 22 patients were operated in supine position according to Valdivia's operative technique. Data were analyzed with t-test. We considered P<0.05 as significant. RESULTS: Surgical complication rate, transfusion rate and fever rate were the same for both groups. Success rate was 72% in supine position group and 63% in prone position group (P>0.05). These results were comparable with the data of the literature. Only operative time was shorter in supine position group with significant statistical difference (P=0.02). CONCLUSION: In our experience, percutaneous nephrolithotomy in the supine position was safe and efficient, and outcomes were similar to that in the prone position. Learning curve was easy and fast.

Evaluation of IPPSE, an alternative method for sequential population PKPD analysis.

The aim of this study is to present and evaluate an alternative sequential method to perform population pharmacokinetic-pharmacodynamic (PKPD) analysis. Simultaneous PKPD analysis (SIM) is generally considered the reference method but may be computationally burdensome and time consuming. Evaluation of alternative approaches aims at speeding up the computation time and stabilizing the estimation of the models, while estimating the model parameters with good enough precision. The IPPSE method presented here uses the individual PK parameter estimates and their uncertainty (SE) to propagate the PK information to the PD estimation step, while the IPP method uses the individual PK parameters only and the PPP&D method utilizes the PK data. Data sets (n = 200) with various study designs were simulated according to a one-compartment PK model and a direct Emax PD model. The study design of each dataset was randomly selected. The same PK and PD models were fitted to the simulated observations using the SIM, IPP, PPP&D and IPPSE methods. The performances of the methods were compared with respect to estimation precision and bias, and computation time. Estimated precision and bias for the IPPSE method were similar to that of SIM and PPP&D, while IPP had higher bias and imprecision. Compared with the SIM method, IPPSE saved more computation time (61%) than PPP&D (39%), while IPP remained the fastest method (86% run time saved). The IPPSE method is a promising alternative for PKPD analysis, combining the advantages of the SIM (higher precision and lower bias of parameter estimates) and the IPP (shorter run time) methods.

Microstructural and conductivity changes induced by annealing of ZnO:B thin films deposited by chemical vapour deposition.

Zinc oxide (ZnO) thin films have attracted much attention in recent years due to progress in crystal growth for a large variety of technological applications including optoelectronics and transparent electrodes in solar cells. Boron (B)-doped ZnO thin films are deposited by low pressure chemical vapour deposition (LPCVD) on Si(100). These films exhibit a strong (002) texture with a pyramidal grain structure. The ZnO films were annealed after growth; the annealing temperature and the atmosphere appear to strongly impact the layer conductivity. This work will first present the modification of the physical properties (carrier concentration, mobility) extracted from the simulation of layer reflection in the infrared range. At low annealing temperatures the mobility increases slightly before decreasing drastically above a temperature close to 250 °C. The chemical and structural evolution (XPS, x-ray diffraction) of the films was also studied to identify the relationship between microstructural modifications and the variations observed in the film conductivity. An in situ XRD study during annealing has been performed under air and low pressure conditions. As observed for electrical properties, the microstructural modifications shift to higher temperatures for vacuum annealing.

Expression analysis of loci associated with type 2 diabetes in human tissues.

AIMS/HYPOTHESIS: Genetic mapping has identified over 20 loci contributing to genetic risk of type 2 diabetes. The next step is to identify the genes and mechanisms regulating the contributions of genetic risk to disease. The goal of this study was to evaluate the effect of age, height, weight and risk alleles on expression of candidate genes in diabetes-associated regions in three relevant human tissues. METHODS: We measured transcript abundance for WFS1, KCNJ11, TCF2 (also known as HNF1B), PPARG, HHEX, IDE, CDKAL1, CDKN2A, CDKN2B, IGF2BP2, SLC30A8 and TCF7L2 by quantitative RT-PCR in human pancreas (n = 50), colon (n = 195) and liver (n = 50). Tissue samples were genotyped for single nucleotide polymorphisms (SNPs) associated with type 2 diabetes. The effects of age, height, weight, tissue and SNP on RNA expression were tested by linear modelling. RESULTS: Expression of all genes exhibited tissue bias. Immunohistochemistry confirmed the findings for HHEX, IDE and SLC30A8, which showed strongest tissue-specific mRNA expression bias. Neither age, height nor weight were associated with gene expression. We found no evidence that type 2 diabetes-associated SNPs affect neighbouring gene expression (cis-expression quantitative trait loci) in colon, pancreas and liver. CONCLUSIONS/INTERPRETATION: This study provides new evidence that tissue-type, but not age, height, weight or SNPs in or near candidate genes associated with increased risk of type 2 diabetes are strong contributors to differential gene expression in the genes and tissues examined.

A pharmacodynamic Markov mixed-effects model for determining the effect of exposure to certolizumab pegol on the ACR20 score in patients with rheumatoid arthritis.

The American College of Rheumatology (ACR) 20% preliminary definition of improvement in rheumatoid arthritis (RA) (ACR20) is widely used in clinical trials to assess response to treatment. The objectives of this analysis were to develop an exposure-response model of ACR20 in subjects receiving treatment with certolizumab pegol and to predict clinical outcomes following various treatment schedules. At each visit, subjects were classified as being ACR20 responders or ACR20 nonresponders or as having dropped out. A Markov mixed-effects model was developed to investigate the effects of the drug on the transitions between the three defined states. Increasing certolizumab pegol exposure predicted an increasing probability of becoming a responder and remaining a responder, as well as a reduced probability of dropping out of treatment. Data from simulations of the ACR20 response rate support the use of dosing regimens of 400 mg at weeks 0, 2, and 4 followed by 200 mg every 2 weeks, or an alternative maintenance regimen of 400 mg every 4 weeks.

[What is the clinical practice of partial nephrectomy in France?]. / Quelle pratique de la néphrectomie partielle en France ?

OBJECTIVE: To describe the practice of partial nephrectomy (PN) in France and assess its results in terms of morbidity and cancer control. MATERIAL AND METHOD: Seven French University Hospitals in which nephron sparing surgery represents at least 30% of the total number of nephrectomies for renal tumour, participated in this study. All centres included, as exhaustively as possible, all their PN cases. For each patient, 70 variables were harvested in order to characterize the patient population, the indications, the operative technique, the per- and postoperative course and complications, the tumor specificities, the carcinologic control and renal function follow-up. RESULTS: Seven hundred and forty-one PN, of which 579 for malignant tumours were analysed. The mean tumour size was 3.4+/-2.1 cm (0.1-18) and 20.8% of the tumours were larger than 4 cm. In 30.1% of cases, the indication was imperative. Among the PN, 12.2% were performed laparoscopically. The mean operating time was 151+/-54.2 min (55-420). The medical and surgical complications rates were respectively 15.2 and 14.7%. At a mean 38 months follow-up, the local recurrence rate was 3.5% and the specific death rate was 4.5%. CONCLUSION: PN is nowadays getting a more and more widely used technique in France. This expansion is completely justified by its results and urologists must consider nephron sparing surgery as the gold standard treatment for renal tumours measuring less than 4 cm.

[Do broader indications for partial nephrectomy result in excess morbidity?]. / Elargir les indications de la néphrectomie partielle induit-il un surcroît de morbidité? Une étude multicentrique française.

OBJECTIVE: To evaluate the morbidity of partial nephrectomy (PN) according to tumour size and the type of indication based on a multicentre retrospective study. MATERIALS AND METHODS: Seven French teaching hospitals participated in this study. Data concerning tumour size, indication for PN (elective or necessity), age, gender, TNM stage, histological type, Fuhrman grade, ASA score and performance status (ECOG) were analysed. Medical and surgical complications, intraoperative blood loss, blood transfusion rate and length of hospital stay were also studied. Statistical analysis of qualitative and quantitative variables was performed with Chi-square test (Fisher's test) and Student t-test. RESULTS: Six hundred and ninety one patients were included. The median tumour diameter was 3cm (0.4-18). Tumours measuring less or equal to 4cm and incidental tumours represented 77.7 and 80.7% of cases, respectively. Clear cell carcinomas represented 75.1% of malignant tumours. Some 89.1% of tumours were T1, 1.6% were N+ and 2.3% were M+. In the 486 elective indications: the operating time (p = 0.03), mean blood loss (p = 0.04), and urinary fistula rate (p = 0.01) were significantly higher in tumours greater than 4cm. These differences were not associated with an increase in the medical (p = 0.7) or surgical complication rate (p = 0.2), or the length of hospital stay (p = 0.4). CONCLUSION: Broader indications for elective PN is associated with an increased morbidity but which remains acceptable. This is an important point for patient information and to guide the choice of surgical strategy, particularly in elderly, frail patients or patients with major comorbidities.

Detection of human immunodeficiency virus type 1 antiretroviral resistance mutations by high-density DNA probe arrays.

Genotypic resistance testing has become an important tool in the clinical management of patients infected with human immunodeficiency virus type 1 (HIV-1). Standard sequencing methodology and hybridization-based technology are the two principal methods used for HIV-1 genotyping. This report describes an evaluation of a new hybridization-based HIV-1 genotypic test of 99 clinical samples from patients infected mostly with HIV-1 subtype B and receiving treatment. This test combines RNA extraction with magnetic silica particles, amplification by nested reverse transcriptase PCR, and detection with high-density probe arrays designed to detect 204 antiretroviral resistance mutations simultaneously in Gag cleavage sites, protease, reverse transcriptase, integrase, and gp41. The nested reverse transcriptase PCR success rates at viral loads exceeding 1,000 copies/ml were 98% for the 2.1-kb amplicon that covers the Gag cleavage sites and the protease and reverse transcriptase genes, 92% for the gp41 amplicon, and 100% for the integrase amplicon. We analyzed 4,465 relevant codons with the HIV-1 DNA chip genotyping assay and the classic sequence-based method. Key resistance mutations in protease and reverse transcriptase were identified correctly 95 and 92% of the time, respectively. This test should be a valuable alternative to the standard sequence-based system for HIV-1 drug resistance monitoring and a useful diagnostic tool for simultaneous multiple genetic analyses.

Efficient in vitro direct shoot organogenesis and regeneration of fertile plants from embryo explants of Bambara groundnut ( Vigna subterranea L. Verdc.).

An efficient protocol has been developed for direct shoot organogenesis from embryo axes derived from mature seeds of two different landraces of Bambara groundnut. Multiple shoots were initiated on several media containing different concentrations and combinations of benzylaminopurine (BAP) or thidiazuron (TDZ). Efficient regeneration occurred when the embryo axes were first plated for 6 days on a medium containing high concentrations of BAP (1 mg/l) and alpha-naphthaleneacetic acid (NAA, 1 mg/l) and then cut transversely and transferred onto a medium containing 1.5 mg/l BAP. Shoot regeneration frequency was 100% and from five to eight shoots per explant were obtained. The importance of using embryo explants and cytokinins in the culture media, with respect to controlling the development of a highly organogenic system, was demonstrated. Histological studies revealed that proliferating buds originated directly from the superficial layers of the explants without an intermediate callus phase. The regenerated shoots were rooted on a medium containing 1 mg/l NAA and then transferred to the greenhouse. Flow cytometric analyses and chloroplast counts of guard cells suggested that the regenerants were diploid. All were morphologically normal and fertile. The short duration, high efficiency and low frequency of somaclonal variation of this system make it well suited for wider biotechnological applications of Bambara groundnut-a neglected and under-utilized crop.

Fatty acid abnormalities in chronic pancreatitis: effect of concomitant diabetes mellitus.

OBJECTIVE: Patients with chronic pancreatitis suffer from malabsorption and nutritional deficiencies. However there is little data available concerning the fatty acid profile in chronic pancreatitis. Diabetes mellitus, a common complication of this disease, could interfere with the metabolism of fatty acids. SUBJECTS: We therefore compared the fatty acid composition of LDL from four groups of male patients with (a) chronic pancreatitis without diabetes (ND-CP; n=12), (b) diabetes secondary to chronic pancreatitis and insulin-treated (CP-D; n=35); (c) type 1 diabetes (n=25); and (d) controls (n=20). RESULTS: The patients in both groups of chronic pancreatitis (ND-CP and CP-D) had lower mean values for linoleic acid than that seen in the type 1 DM and control groups, whereas monounsaturated fatty acids (MUFA; 18 : 1(n-9) and (16 : 1(n-7)) were significantly increased in these two groups (ND-CP and CP-D). Docosa-hexaenoic-acid (22 : 6(n-3)) was significantly decreased in the CP-D group (P>0.05), a response that could be explained by the effects of diabetes mellitus and by selenium deficiency. In this way, diabetes was associated with a decrease in the docosa-hexaenoic-acid (22 : 6(n-3); r=0.30, P=0.005), and selenium was correlated with DHA (r=0.28, P=0.029) and with the 22 : 6(n-3)/20 : 5(n-3) ratio (evaluating the delta 4 desaturation); r=0.31, P=0.022), independently of the diabetes effect. Selenium was negatively correlated with 20 : 4(n-6)/20 : 3(n-6) ratio (evaluating the delta 5 desaturase; r=-0.30; P=0.025). These results suggest that these two factors may have a role in the regulation of the desaturation process. If we consider that a ratio of 16 : 1(n-7)/18 : 2(n-6) greater than 0.086 in plasma indicates an EFAn-6 deficiency, 40% of our CP patients, 57.6% of CP-D patients and 13.6% of type 1 DM patients were involved. CONCLUSIONS: The consequences of these deficiencies are not evaluated in this disease. However, correction of the fundamental deficiencies in essential fatty acids and in selenium seems desirable in chronic pancreatitis.

Haemostasis in relation to dietary fat as estimated by erythrocyte fatty acid composition: the prime study.

We investigated whether haemostatic variables were related with dietary fatty acid composition as estimated by the fatty acid content of erythrocytes. Subjects were a subsample (n=283) of the participants in the Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study. Factor VII, fibrinogen, tissue-type plasminogen activator antigen (tPA-ag), plasminogen activator inhibitor type 1 (PAI-1), D-dimer and von Willebrand factor (vWf) were measured and the fatty acid composition was determined in the phospholipids of total erythrocytes by gas chromatography. Statistical analyses were performed using multiple linear regression analyses with adjustment for age, center and body mass index. tPA-ag was significantly related to the n-3 fatty acids derived from fish. This was reflected in an inverse association of all n-3 fatty acids combined with tPA-ag (beta=-0.37 ng/ml/%, 95% confidence intervals: -0.45, -0.29, P<.01). Positive and significant associations of D-dimer with arachidic and eicosamonoenoic acid were observed (P<.01). No relationships were found between fatty acids and fibrinogen, vWf, PAI-1 or factor VII. The results of this study suggest that consumption of n-3 fatty acids derived from fish may favourably influence tPA-ag.

Measurement of apolipoprotein B concentration in plasma lipoproteins by combining selective precipitation and mass spectrometry.

The measurement of apolipoprotein B (apoB) in purified lipoproteins by immunological assays is subject to criticism because of denatured epitopes or immunoreactivity differences between purified lipoproteins and standard. Chemical methods have therefore been developed, such as the selective precipitation of apoB followed by quantification of the precipitate. In this study, we present the measurement of apoB concentration in lipoproteins purified by ultracentrifugation by combining isopropanol precipitation and gas chromatography/mass spectrometry. Very low density lipoprotein (VLDL; d < 1.006 g/mL); VLDL plus intermediate density lipoprotein (VLDL + IDL; d < 1.019 g/mL); and VLDL, IDL, and low density lipoprotein (VLDL + IDL + LDL; d < 1.063 g/mL) were purified by ultracentrifugation. Apolipoprotein B-100 was selectively precipitated by isopropanol. The leucine content of the pellet was then determined by gas chromatography/mass spectrometry, using norleucine as internal standard. Knowledge of the number of leucine molecules in one apoB-100 molecule makes it possible to calculate the plasma concentration of apoB in the various lipoprotein fractions. ApoB in IDL (d 1.006-1.019 g/mL) and LDL (d 1.019-1.063 g/mL) were then determined by subtracting VLDL-apoB from apoB in lipoproteins d < 1.019 and apoB in lipoproteins d < 1.019 g/mL from apoB in lipoproteins d < 1.063 g/mL, respectively. The isopropanol precipitate was verified as pure apoB (>97%) in lipoprotein fractions isolated from normo- and hyperlipidemic plasma and the method appeared reproducible. The combination of isopropanol precipitation and the GC/MS method appears therefore to be a precise and reliable method for kinetic and epidemiological studies.

Metabolism of apolipoproteins AI and AII in subjects carrying similar apoAI mutations, apoAI Milano and apoAI Paris.

ApoAI Milano (AI(M)) and apoAI Paris (AI(P)) are mutant forms of apoAI in which cysteine is substituted for arginine at residues 173 and 151 respectively leading to the formation of homodimers and heterodimers with apoAII. Heterozygous subjects with these mutants are characterized by low levels of plasma HDL cholesterol and apoAI. The present study analyzed the metabolism of the different complexes of apoAI in three subjects, two AI(M) and one AI(P), using a primed-constant infusion of trideuterated leucine. In AI(M) carriers, the mutant form was almost equally distributed in AI(M) dimer, AI(M):AII heterodimer and the monomer, whereas, in the AI(P) subject, the mutant apoAI was essentially in the apoAI(P):AII complex. Normal apoAI was low in the AI(M) subjects (20 and 16 mg/dl) but very low in the AI(P) subject (0.3 mg/dl). In the AI(M) subjects, the low levels of apoAI were due to a rapid catabolism with a normal synthetic rate. However, the apoAI kinetics were heterogeneous with a rapid catabolism of the AI(M):AII complex (FCR of 0.430 and 0.401 day(-1)) and the AI(M) monomer (FCR of 0.570 and 0.406 day(-1)) whereas the AI(M) dimer was catabolized slowly (FCR of 0.114 and 0. 118 day(-1)). In contrast, AI(P) was catabolized relatively slowly with a FCR of 0.263, 0.182 and 0.258 day(-1) for AI(P) homodimer, apoAI(P):AII heterodimer and AI(P) monomer. In the three subjects, normal apoAI was catabolized quickly, with an FCR of 0.805 and 0.601 day(-1) in AI(M) carriers and 0.526 day(-1) in the AI(P) carrier. Therefore, the low level of apoAI in the AI(P) carrier is caused by a low production rate of apoAI, particularly of normal apoAI. In conclusion, apoAI is kinetically heterogeneous in AI(M) and in AI(P) subjects. Moreover, the two mutations lead to significant differences in the kinetic behavior of mutant apoAI depending on its inclusion in its complexes.

Moderate red wine consumption in healthy volunteers reduced plasma clearance of apolipoprotein AII.

BACKGROUND: The mechanisms of the positive relationship between alcohol intake and plasma concentration of high-density lipoprotein (HDL) are still unclear. The present study shows the metabolism modifications of apolipoprotein (apo) AI and apoAII in normolipidaemic healthy volunteers after a period of moderate red wine consumption. DESIGN: Five non-smoking male subjects were studied at the end of two consecutive 4-week periods, one without alcohol and the other with an intake of 50 g per day of alcohol, in random order. The metabolic parameters of apoAI and apoAII in HDL were determined after endogenous labelling using amino acid labelled with stable isotope. Cholesterol, triacylglycerols, HDL-cholesterol, apoAI, apoAII, LpAI, LpAI:AII were determined in plasma at the end of the two study periods. RESULTS: Cholesterol and triacylglycerols did not vary significantly during the two periods, whereas HDL-cholesterol increased from 43.8 to 50.0 mg dL-1 (P < 0.05). ApoAI and apoAII increased significantly (20% and 60% respectively) after the diet was supplemented with alcohol. LpAI:AII increased from 73.8 to 101.6 mg dL-1 (+32%) (P < 0.05), whereas alcohol had no effect on the concentration of LpAI. The alcohol treatment did not significantly alter the metabolism of apoAI. Conversely, the fractional catabolic rate of apoAII decreased significantly by 21% (P < 0.05) with alcohol, whereas the production rate of apoAII tended to increase by 18% (P = 0.08). CONCLUSION: The decrease in the fractional catabolic rate of apoAII could lead to an accumulation of apoAII-containing lipoproteins in plasma and account for the dramatic increase in LpAI:AII observed in the plasma of subjects consuming alcohol.

Quantitative analysis of cholesterol and cholesteryl esters in human atherosclerotic plaques using near-infrared Raman spectroscopy.

Raman spectroscopy is a non-destructive analytical technique and previous results have shown that qualitative analysis of the lipid component of human atheromatous arteries is feasible. In this paper, we describe a quantitative analytical method for cholesterol and cholesteryl esters in human atherosclerotic plaques, combined with Raman spectroscopic results, using partial least-squares (PLS) regression, a statistical multivariate method based on factorial analysis. Twenty-nine human atherosclerotic pooled samples were studied and the results of Raman spectroscopy coupled with the PLS method were compared to biochemical results. The standard error of prediction was 16.1, 13.6, 1.9, 3.3 and 3.4 mg/g for total cholesterol, free cholesterol, palmitate cholesteryl, oleate cholesteryl and linoleate cholesteryl, respectively. The repeatability of Raman spectroscopy was found to be excellent. Our results show that Raman spectroscopy is a promising technique to obtain a consistent and non-destructive quantitative analysis of cholesterol and cholesteryl esters in human atherosclerotic lesions. In situ and in vivo analysis is a possibility in the near future.