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The behavioral goals of the coronary patient require active management by the cardiologist. Every smoker must be clearly informed about the cardiovascular consequences of smoking and the major benefits of smoking cessation. The only advice to "quit smoking" is not enough. Validated "treatments" (cognitive-behavioral therapy, nicotine replacement therapy, varenicline, bupropion) must be used, with a precise strategy and prolonged follow-up. All drugs assistance can be prescribed in coronary patients and nicotine replacement therapy can even be used just after a myocardial infarction. Nutrition plays a significant role in cardiovascular prevention. Counseling today is based on solid evidence, although evidence is harder to obtain than with drugs. It should no longer be advisable only to "suppress cooked fats and starches" because these recommendations are unclear and/or false. Today we need positive food-based benchmarks and complex dietary patterns in which fruits and vegetables, fish, whole grains, pulses, nuts, olive oil and a diet closed to the Mediterranean diet. Dairy products have their place. Sugary foods should be limited especially in case of overweight and metabolic syndrome. Physical activity is part of good nutrition. Indeed, the fight against a very sedentary lifestyle and physical inactivity in coronary and heart failure patients is part of the lifelong treatment of these patients. The cardiologist and the general practitioner must be much more involved in their prescription and education to hope for good compliance.

The burden of hypoglycaemia is important, particularly in elderly type 2 diabetes (T2D) patients. Unfortunately, however, few studies are available concerning this population. GERODIAB is a prospective, multicentre, observational study that aims to describe the 5-year morbidity and mortality of 987 T2D patients aged 70 years and older. After analyzing the frequency of and factors associated with hypoglycaemia in the 6 months prior to study inclusion, it was found that hypoglycaemia was associated with retinopathy, lower levels of LDL cholesterol and altered mini-Geriatric Depression Scale (GDS) scores.

Providing well-being and maintaining good health are main objectives subjects seek from diet. This manuscript describes the development and preliminary validation of an instrument assessing well-being associated with food and eating habits in a general healthy population. Qualitative data from 12 groups of discussion (102 subjects) conducted with healthy subjects were used to develop the core of the Well-being related to Food Questionnaire (Well-BFQ). Twelve other groups of discussion with subjects with joint (n = 34), digestive (n = 32) or repetitive infection complaints (n = 30) were performed to develop items specific to these complaints. Five main themes emerged from the discussions and formed the modular backbone of the questionnaire: "Grocery shopping", "Cooking", "Dining places", "Commensality", "Eating and drinking". Each module has a common structure: items about subject's food behavior and items about immediate and short-term benefits. An additional theme - "Eating habits and health" - assesses subjects' beliefs about expected benefits of food and eating habits on health, disease prevention and protection, and quality of ageing. A preliminary validation was conducted with 444 subjects with balanced diet; non-balanced diet; and standard diet. The structure of the questionnaire was further determined using principal component analyses exploratory factor analyses, with confirmation of the sub-sections food behaviors, immediate benefits (pleasure, security, relaxation), direct short-term benefits (digestion and satiety, energy and psychology), and deferred long-term benefits (eating habits and health). Thirty-three subscales and 14 single items were further defined. Confirmatory analyses confirmed the structure, with overall moderate to excellent convergent and divergent validity and internal consistency reliability. The Well-BFQ is a unique, modular tool that comprehensively assesses the full picture of well-being related to food and eating habits in the general population.

Age-related macular degeneration is a growing burden disease with a high prevalence in elderly: it is the first cause of blindness in developped countries. It is a multifactorial disease with genetic factors and nutritional factors. Carotenoids, lutein and zeaxanthin are components of macular pigment and they have a filter role for blue light and an antioxidant role. Other nutritional factors might play a role as antioxidants: zinc, selenium, vitamin E, vitamin C… which lead to the ARED Study. It is the only one study with proven positive effects on the disease progression (stages 3 and 4). A high glycemic index increases oxidative stress. Long chain omega-3 polyunsaturated fatty acids have a protective effect. Available data are presented and discussed. These are new preventive issues.

Vingt-six jeunes adultes, en surpoids et obeses, ont beneficie d’une prise en charge de leur probleme ponderal a partir d’un sejour thermal specifiquement elabore pour eux a Brides-les-Bains. Un suivi par Internet et un sejour de rappel effectue a six mois ont permis une evaluation a moyen terme. Les resultats sont encourageants tant sur le plan ponderal que sur le plan physique et psychologique.

L’observation clinique suggere que le stress ait un impact sur la prise de poids. Cet article fait le point sur les donnees cliniques, epidemiologiques, experimentales et mecanistiques recentes. Le stress peut favoriser une prise alimentaire, surtout chez les sujets restreints. La prise de poids est surtout abdominale pouvant conduire a un syndrome metabolique et a un risque cardiovasculaire accru. La stimulation de l’axe hypothalamo-hypophysosurrenalien et la synthese dans le tissu adipeux de cortisol ainsi que la stimulation du systeme sympathique sont les mecanismes habituellement reconnus. Des voies de prevention sont evoquees, notamment l’effet possible des acides gras omega-3 a longue chaine sur certains points d’impact.

Resume Perdre du poids est une preoccupation importante pour les sujets obeses (OB) ou en surpoids (SP). Quels moyens mettent en œuvre les personnes qui decident de maigrir ?

Resume Peu de travaux prennent en consideration les sujets en surpoids en dehors des circuits de consultation. Ce travail vise a mieux connaitre le vecu de ces sujets, tant leur souffrance, les causes percues de la prise de poids, que leur representation de la perte de poids.

International audience; Objectives To develop and validate an instrument assessing well-being associated with food and eating habits in a general healthy population, suitable for future food allegation support. Providing well-being and maintaining good health are two main objectives subjects seek from their diet. To date validated questionnaires measuring well-being in the specific context of food in general population do not exist. Methods Thorough standardized methodology was followed. Qualitative data from 24 discussion groups conducted with healthy subjects (n=102) and subjects with digestive, joint or immunity complaints (n=96) served to develop the core of the Well-Being related to Food Questionnaire (Well-BFQ). Preliminary validation was conducted with 444 subjects with balanced diet (n=81), non-balanced diet (n=65), or standard diet (n=298). Principal component analyses (PCA) and exploratory factor analyses were performed sequentially to reduce the number of items and determine the questionnaire structure. Confirmatory factor analyses with multi-trait analyses were carried out to confirm its structure. Results The validated structure of the Well-BFQ has a modular backbone composed of “Grocery shopping”, “Cooking”, “Dining places”, “Commensality”, “Eating and drinking” and “Eating habits and health”. Each module is measured in terms of food behaviour and benefits: immediate, (Pleasure, Security, and Relaxation); direct and short term (Digestion and Satiety, Energy and Psychology); deferred (Metabolism, Mood and energy, Ageing, Bowel movement, Immunity and Mobility). PCA defined 33 interpretable subscales and 15 single items. Internal consistency reliability of dimensions was very good (Cronbach’s alpha: 0.75-0.95). Item convergent validity and divergent validity were moderate to excellent. Conclusions The Well-BFQ is unique to assess the full picture of well-being related to food and eating habits in terms of immediate, direct and short and deferred benefits in general population. Its modular structure allows interdisciplinary users to address their specific research (including experimental, cross-cultural comparison studies) needs by selecting the module(s) relevant to their objectives.

International audience; Objectives To document the external validation of the Well-Being related to Food Questionnaire (Well-BFQ) by studying variations of scores according to subjects’ nutritional status. The Well-BFQ was developed after conducting interviews with healthy subjects and subjects with digestive, joint or immunity complaints. Its structure was determined using principal component analyses and confirmed using factor analyses with multi-trait analyses. Methods The Well-BFQ has a modular backbone with sub-dimensions measuring pleasure, security, relaxation, digestion and satiety, energy and psychology, health (ageing, bowel movement, immunity and mobility) and food behaviour. Each sub-dimension is rated from 0 to 100; distributions were compared according to the nutritional status of the subjects using variance analyses. Nutritional status was evaluated according to the PNNS questionnaire (French National Health Nutritional Program). Results Subjects (N=444) were aged 42±15 years and 71.6% women; 18.1% had a balanced diet (BD), 14.7% a non-balanced diet (NBD) and 67.1% a standard diet (SD). The majority of the dimensions assessed with the Well-BFQ were significantly higher (i.e. better food-related well-being) in subjects with a BD than in those with a NBD; even the dimensions assessing commensality (eating as a group) and behavioural attitudes toward buying and cooking food. In particular, the security dimension was rated 67.9±19.5 in BD compared with 56.9±25.2 in NBD and 61.1±21.3 in SD (pConclusions This study contributes to the external validity of Well-BFQ by demonstrating the expected positive correlation of the well-being it measures and the quality of the diet of the subjects. Its ability to measure well-being differences according eating habits makes it a promising tool for epidemiological surveys and experimental trials.

Resume La cataracte est, a cote de la degenerescence maculaire liee a l'âge, une pathologie oculaire degenerative dont la prevalence augmente du fait du vieillissement de la population. C'est la premiere cause de cecite mondiale avec 25 millions de cas. En France, 400 000 cataractes sont operees chaque annee. A partir de 75 ans, on estime que plus de la moitie de la population americaine presente des opacites cristalliniennes ou une cataracte cliniquement significatives. Depuis plus de 20 ans, des etudes suggerent que des facteurs nutritionnels pourraient, a travers le stress oxydatif, et en complement des facteurs d'environnement classiques comme l'exposition aux ultraviolets et au tabac, jouer un role dans la survenue ou a l'inverse dans la protection vis-a-vis du risque de cataracte.

Resume Le stress oxydatif et l'equilibre des familles d'acides gras poly-insatures a longue chaine pourraient etre impliques au cours des hypertonies oculaires et du glaucome. Ainsi, des facteurs nutritionnels pourraient moduler le cours de la maladie. Le statut vis-a-vis du stress oxydatif provoquerait des modifications de la matrice extracellulaire du trabeculum. D'une part des reactions d'apoptose et de remodelage du collagene (associees a l'augmentation de la pression intraoculaire) sont principalement influencees par les antioxydants hydrosolubles tels que le glutathion, d'autre part, des reactions d'apoptose et de remodelage de l'elastine (correlees a la survenue de l'atrophie optique) sont surtout influencees par les antioxydants liposolubles tels que la vitamine E. Par ailleurs, le ratio alimentaire des acides gras omega-3/omega-6 de l'alimentation pourrait moduler l'equilibre de la pression intraoculaire. Les acides gras de la famille omega-3 exercent une certaine competition vis-a-vis de la cyclo-oxygenase. Un regime riche en omega-3 et pauvre en omega-6 pourrait alors favoriser une augmentation de la pression intraoculaire par defaut de synthese de la prostaglandine (PG) F2 et par diminution relative du drainage uveoscleral. L'importance reelle de ces facteurs reste mal determinee actuellement, mais a fait l'objet d'un certain nombre de publications. Des etudes sont en cours pour preciser l'implication reelle de ces facteurs nutritionnels.

Resume La pathogenie de la degenererescence maculaire liee a l'âge (DMLA) fait intervenir des facteurs nutritionnels lies au stress oxydant. En effet, les micronutriments antioxydants, les antiradicalaires ou les micronutriments protegeant de la lumiere bleue jouent un role dans la protection vis-a-vis de la maladie. Ces facteurs nutritionnels sont intriques avec des facteurs environnementaux tels que le tabagisme ou l'exposition chronique a la lumiere bleue. Les donnees experimentales et epidemiologiques sont maintenant concordantes et coherentes, mais le role protecteur de ces micronutriments antioxydants et surtout la dose utile et depourvue d'effets secondaires restent incompletement etablis. Par ailleurs, les etudes d'intervention comportant une supplementation en acides gras poly-insatures a longue chaine (AGPI) de la famille omega-3 (acide docosahexanoique [DHA]) representent aussi une avancee importante pour la prevention primaire de la maladie. En pratique, une supplementation en AGPI omega-3 pourrait etre proposee chez certains sujets a risque de DMLA a titre de prevention primaire et une supplementation comportant un cocktail de micronutriments antioxydants et protecteurs de la lumiere bleue pourrait etre proposee a des patients presentant une DMLA aux stades 3 et 4, ou a des sujets ayant un desequilibre nutritionnel a titre de prevention secondaire. Ces eventuelles supplementations sont bien entendu compatibles avec des conseils alimentaires simples. Une meilleure formulation et une optimisation de la dose des supplements actuellement proposes pourraient accroitre leur interet. De nouvelles recherches et de nouvelles etudes cliniques restent necessaires pour valider definitivement ces formulations et peut-etre leur permettre d'acceder au statut de medicament.

Resume La degenerescence maculaire liee a l’âge (DMLA) est une affection dont la prevalence est importante chez les sujets âges; elle represente une cause majeure de malvoyance. C’est une affection multifactorielle, avec des facteurs non modifiables (âge, genetique…) et des facteurs modifiables en particulier nutritionnels. Les carotenoides xantophylles sont les elements constitutifs du pigment maculaire et exercent un role de filtre de la lumiere bleue, et un role antioxydant. D’autres facteurs nutritionnels pourraient intervenir comme antioxydants: zinc, selenium, vitamine E, vitamine C, ce qui a conduit a l’etude AREDS. Il s’agit de la seule etude ayant aujourd’hui montre des resultats favorables avec une diminution du risque de progression de la maladie au stade 3 et au stade 4. Un index glycemique eleve augmente le stress oxydatif. Enfin, les acides gras polyinsatures omega-3 a longue chaine exercent un effet protecteur. Les donnees disponibles sont presentees et discutees. Ce sont des pistes de prevention importantes.

Un des atouts nutritionnels du poisson est incontestablement sa richesse en acides gras poly-insatures de la famille des omega 3. Ceux-ci sont aujourd'hui reconnus comme ayant un role benefique pour la sante, en particulier en terme de prevention des maladies cardiovasculaires. Cependant, plusieurs travaux rapportent que les procedes de conservation peuvent alterer ces acides gras. C'est en particulier le cas pour la congelation ou le fumage. Par contre, l'appertisation peut permettre une bonne preservation de l'EPA (acide eicosapentaenoique) et du DHA (acide docosahexaenoique), acides gras omega 3 caracteristiques du poisson. Etant donnes d'une part l'interet pour la sante de ces acides gras omega 3 et leur fragilite d'autre part, il semble necessaire d'optimiser les procedes de conservation du poisson pour preserver au mieux son interet nutritionnel et son atout sante.

Objective: To compare the costs of treating hypercholesterolaemic patients to a modified European Atherosclerosis Society low density lipoprotein cholesterol (LDL-C) target using atorvastatin, fluvastatin, pravastatin and simvastatin.

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since jeudi 31 octobre 2013

To investigate the autoantibody repertoire associated with SLE, we have created phage display IgG Fab libraries from two clinically active SLE patients and from the healthy identical twin of one of these patients. The libraries from the lupus discordant twins were found to both include unusually large representations of the V(H)5 gene family. By panning with DNA, the SLE libraries each yielded IgG anti-double-stranded (ds) DNA autoantibodies, which are characteristic of lupus disease. These included a V(H)5 autoantibody from the affected twin, that has a targeted cluster of mutations that potentially improves binding affinity. The recovered IgG anti-dsDNA autoantibodies expressed the same idiotypes associated with the in vivo IgG anti-dsDNA response of the respective SLE donor. Heavy-light chain shuffling experiments demonstrated a case in which the in vitro creation of anti-dsDNA binding activity required restrictive pairing of a heavy chain with Vlambda light chains similar to those in circulating anti-dsDNA autoantibodies. By contrast, IgG anti-ds autoantibodies could not be recovered from the library from the healthy twin, or from shuffled libraries with heavy chains from the healthy twin. These repertoire analyses illustrate how inheritance and somatic processes interplay to produce lupus-associated IgG autoantibodies.

The surrogate light chain, composed of VpreB and lambda 5/14.1 proteins, is selectively expressed on B cell precursors, and is important for B cell development. The surrogate light chain associates with cell surface mu-chains on preB cells, but little is known about the ligand specificity and affinity of VpreB binding. To analyze its interactions with Igs, we made recombinant human VpreB protein and measured its affinity for H and L chain V domains using surface plasmon resonance. The recombinant VpreB protein existed as a homodimer in solution. VpreB chains associated with each other with an apparent Kd = 5 x 10(-7) M, and bound to a human VH domain, a mouse VH domain, and a human VL domain with a similar affinity. VpreB protein also bound to human Fab fragments of IgG with an apparent Kd = 6 x 10(-7) M, but showed a very low affinity for human Fc fragments of IgG. VpreB-Fab complex formation was reproduced by the formation of a trimolecular VpreB-VH-VL complex. Thus, VpreB proteins can associate with each other and also form complexes with Ig at sites different from those involved in VH-VL interaction. By flow cytometry, biotinylated VpreB protein bound to surface Ig-positive B cells but not T cells. Receptors that contain VpreB could be cross-linked by either Ig or by self-association.

Anthracycline accumulation was evaluated by flow cytometry or radiolabeled drug assays in cells and cytoplasts (enucleated cells) prepared from parental and multidrug-resistant human K562 leukemia cells. Treatment with energy inhibitors, such as dinitrophenol (DNP) or sodium azide/deoxyglucose, led to a marked decrease in daunorubicin accumulation in parental cells and cytoplasts. Another ionophore, monensin, also caused a significant decrease in daunorubicin accumulation; however, ATPase inhibitors ouabain, vanadate, and N-ethylamaleimide had little or no effect. The lysosomatropic agents chloroquine and methylamine caused a moderate decrease in anthracycline accumulation. Fluorescence microscopy showed that the DNP-sensitive daunorubicin uptake occurred in a nonnuclear subcellular compartment. Studies using increasing daunorubicin concentrations demonstrated fluorescence quenching that occurred in the nonnuclear, DNP-sensitive compartment. The effect of inhibitors on the accumulation of rhodamine 123 and acridine orange strongly implicated lysosomes as the principal compartment of this inhibitable daunorubicin accumulation. Cytoplasts from P-glycoprotein containing multidrug-resistant K562 cells demonstrated a verapamil-reversible, decreased daunorubicin accumulation that was observed in resistant whole cells. Verapamil pretreatment of cytoplasts from resistant cells revealed the subcellular DNP-sensitive uptake present in parental cytoplasts. These studies demonstrate that cytoplasts are an effective means to study drug transport in mammalian cells without nuclear drug binding. Parental K562 cells and cytoplasts exhibit an energy-dependent accumulation of daunorubicin into cytoplasmic organelles that is also present in resistant cells and cytoplasts when P-glycoprotein mediated efflux is inhibited.

Age-related macular degeneration is a growing burden disease with a high prevalence in elderly: it is the first cause of blindness in developped countries. It is a multifactorial disease with genetic factors and nutritional factors. Carotenoids, lutein and zeaxanthin are components of macular pigment and they have a filter role for blue light and an antioxidant role. Other nutritional factors might play a role as antioxidants: zinc, selenium, vitamin E, vitamin C… which lead to the ARED Study. It is the only one study with proven positive effects on the disease progression (stages 3 and 4). A high glycemic index increases oxidative stress. Long chain omega-3 polyunsaturated fatty acids have a protective effect. Available data are presented and discussed. These are new preventive issues.

Report # 8 of the Age Related Eye Disease Study (AREDS) showed the interest of a cocktail of antioxidant micronutrients for the uni- or bilateral intermediate forms and the unilateral evolved forms of Age related Macular Degeneration. This use of supranutritional amounts aiming at obtaining a therapeutic effect corresponds to the concept of "neutraceuticals" which can be opposed to the concept of nutritional amounts. Although the AREDS was carried out under strict conditions, the evolution of knowledge in micronutrition since its design has led to some criticism of both the amounts of the micronutrients and the composition of the formulation. For example several authors pointed out that beta-carotene used at 3 fold the daily recommendations could have harmful effects, especially among smokers or former smokers. Other authors pointed out that vitamin E, at amounts corresponding to 40 to 60 fold the amounts recommended could be correlated with a lethal risk. We develop here some notions about safety and/or harmlessness of the antioxidant micronutrients.

1Mapi, Lyon, France ; 2Cenbiotech, Dijon, France ; 3INRA UMR 1286 Universite Bordeaux II, Bordeaux, France ; 4Laboratoire CERTOP (UMR CNRS 5044) et departement ISTHIA Universite de Toulouse II le Mirail, Toulouse, France ; 5Laboratoire d'Experimentation en Sciences Sociales et Analyse des Comportements ESC Dijon Bourgogne, Dijon, France ; 6Institut Pasteur de Lille Service de Nutrition, Lille, France ; 7Lara Spiral, Dijon, France ; 8Danone, Palaiseau, France ; 9Laboratoire Parisien de Psychologie Sociale Universites de Paris 8 & Paris 10, Paris, France

The burden of disorders associated with overweight and obesity is a major public health problem. It is therefore important to better identify these concomitant disorders and how their frequencies vary with sex and age.A survey was carried out during a 5 month-period from September 2001 to January 2002) among 4 727 general practitioners distributed throughout France in 18 102 patients with a body mass index (BMI)25 kg/m2. The practitioners evaluated the presence of concomitant disorders using a closed questionnaire. The patients assessed global discomfort linked to overweight using an analog visual scale. Univariate and multivariate analyses of the concomitant disorders and self-reported discomfort depending on age, gender and BMI were performed.The survey population comprised 66.8% of women (W) and 33.2% of men (M). Mean age was 48.0 +/- 13.2 years and mean BMI was 34.6 +/- 6.1, with no differences between the two sexes. The most frequent concomitant disorders were back pain (44.6%), hypertension (44.2%), dyslipidemia (39.9%), knee osteoarthritis (30.8%), lower limb edema (24.3%), hypersudation (23.8%), skin fold mycosis (22.8%) and type 2 diabetes (21.6%). In multivariate analyses, the distribution of these disorders varied with sex: hypertension, type 2 diabetes, dyslipidemia, and hypersudation were more frequent in men, whereas knee osteoarthritis, back pain, and skin fold mycosis were more frequent in women. The prevalence (odd ratio, OR) of back pain and dyslipidemia did not increase with higher BMI and the prevalence of back pain did not increase with age. Overall discomfort related to overweight was rated as 61.3 +/- 19.9 mm on a 0 to 100-mm scale. Discomfort was less marked in men, decreased with age and increased with BMI (and with the consultations in the Paris area).This study shows the complexity of relationships between concomitant diseases, overall discomfort, BMI, age and sex (in the population of overweight and obese patients) and should improve the management of such patients and their complications.

The genome structure and expression of mdr genes were examined in multidrug-resistant sublines of two different murine (DBA/2J) Friend erythroleukemia cell lines, PC4 and C7D, derived by stepwise exposure to increasing concentrations of adriamycin beginning with 5 ng/ml. The PC4 cell lines selected in higher drug concentrations (80-1280 ng/ml) demonstrated amplification of all three mdr genes with preferential amplification of mdr3. Overexpression of the mdr2 and mdr3 genes accompanied their genomic amplification; however, expression of mdr1 was not seen despite amplification. In the C7D cell lines selected with higher drug concentrations (40-160 ng/ ml), amplification and overexpression of mdr1 and mdr2 without mdr3 was observed. Increased expression of mdr1 occurred prior to gene amplification. The distribution of mdr-specific genes in micrococcal nuclease-generated chromatin fractions differing in transcriptionally active sequences and proteins was different between the parent and drug-resistant sublines. An enrichment (two- to threefold) of mdr3 genes in the H1-depleted mononucleosome fraction enriched for actively transcribed genes (e.g., globin) was detected by Southern analysis of chromatin fractions in PC4-80 cells (selected in 80 ng/ml of adriamycin and overexpressing mdr3), compared to the parental cells. mdr3 enrichment was also detected using a new PCR-based method, which examined mdr3 genes and repetitive sequences. Of note, the H1-depleted chromatin fraction from PC4-20 showed enrichment of the mdr3 gene, although mdr3 expression was not detected in the cell line. These studies showed a different pattern of gene amplification and overexpression in genetically related erythroleukemia cell lines selected for resistance to the same chemotherapeutic agent. A change in chromatin organization of mdr genes preceded overexpression and amplification of the mdr3 gene.

The android pattern of body fat distribution has been shown to increase the risk of metabolic and coronary heart disease. Protective lipid markers against cardiovascular disease were studied in 98 obese normolipidaemic, non diabetic, non-smoker subjects over 18 years of age according to regional distribution of adipose tissue as estimated by the waist ship ratio (WHR) and overall obesity as estimated by the body mass index (BMI). WHR was inversely correlated with Lp AI (r = 0.46) and HDL-cholesterol (r = 0.37). BMI was not correlated with protective lipid parameters but only with triglycerides. After adjustment, Lp AI was lower in men and in upper body obese women (p0.05). Lp AI is a better indicator of body fat distribution than HDL-cholesterol or apo AI, and its variations appear to be indirectly related to gender, menopause, and age, thereby influencing body fat distribution (the main factor accounting for Lp AI variation). Lp AI was inversely correlated with WHR in gluteal-femoral obese women but not in abdominally obese women or men, possibly because of a threshold effect.

Antibodies H241 and 2C10 are lupus mouse IgG autoantibodies that bind native DNA. In previous experiments, oligonucleotide antigens affinity-labeled both H and L chains of H241 but only the H chain of antibody 2C10. Primary structures of the V regions of the 2C10 H and L chains and the H241 L chain, determined from cDNA, help to explain the previous affinity-labeling experiments. The 2C10 L chain CDRs had several Asp residues and a net negative charge of five, whereas the 2C10 H chain CDRs had four Arg residues and a net positive charge of five. The L chain CDRs of H241 had a net positive charge of one. [The H241 H chain cDNA sequence was published previously by Gangemi et al. (1993) J. Immun. 151, 4660–4671]. Plasmid vectors were used for bacterial expression of H and L chains of 2C10 alone and in combinations in single chain Fv (scFv) molecules. The H chain alone bound native DNA as well as or better than the H-plus-L chain scFv. The H chain alone also bound Z-DNA. Combination of the 2C10 H chain with the L chain of an anti-Z-DNA antibody maintained the selectivity for Z-DNA, whereas its combination with the 2C10 L chain (in the 2C10 Fab) yielded selective B-DNA binding. The results with 2C10 match other examples in which the H chain is sufficient for DNA binding but selectivity is modulated by the L chain. The H chain binding to autoantigen may reflect selective events in early stages of B cell development.

An outline of the points of impact of atherothrombosis on pathophysiological processes is followed by a review of nutritional trials concerning the prevention and regression of atherosclerosis. Unifactorial primary prevention studies, although favourable overall, are subject to methodological criticisms and would require far larger cohorts before conclusions can be drawn. Multifactorial primary prevention studies show evidence of efficacy proportional to the reduction in risk factors obtained. The OSLO study is the most conclusive in this respect. Secondary prevention studies concern patients with coronary disease or infarct survivors. They are extremely heterogeneous. Certain involve nutritional supplements in addition. Others, such as the Renaud study based upon a mediterranean-type diet, are spectacular. Trials of the prevention by n-3 fatty acids of restenosis after transluminal coronary angioplasty are also analysed: 5 out of 8 were effective. All studies devoted to the regression of atherosclerosis have revealed less progression or regression of the disease following nutritional measures, on the basis of both clinical and angiographic parameters. The role of nutrition in the prevention and treatment of atherothrombosis is worthy of greater consideration on a first-line basis, before being completed by drug treatment, the efficacy of which is then enhanced.

Atherosclerosis is a process in which lipid and factors are mixed. When LDL are oxydized, they are catabolized by the macrophage's pathway, leading to foam cells which constitute the fatty streak, the earliest lesion in atherogenesis, and they have cytotoxic, chemotactic effects. Many protective devices against free radicals and oxydation mechanisms exist, particularly antioxydant vitamins and other natural dietary antioxydants. After a brief recall of their mechanisms, epidemiological, experimental and clinical data are reviewed. To day it seems necessary to take into consideration these factors in prevention and therapeutic of atherosclerosis and dylipidaemia. Many inquiries keep going, particularly about susceptible of LDL to oxydation. One is waiting for intervention surveys in order to conclude about nutritional and medical treatments.

The efficacy on plasma lipids, apo A1 and B of a HMG Co A Reductase inhibitor, simvastatin, and a fibrate derivative, gemfibrozil, were compared in 136 hypercholesterolemic patients. The study was randomized, double-blinded and the active drug was given after a 4 week period of placebo. Gemfibrozil (n = 69) was given at 900 mg q.p.m. during the entire study. The primary dose of simvastatin was 10 mg q.p.m. during the first 6-weeks of treatment. At the end of this period, the dose was doubled if the cholesterol level was above 2 g/l (5,16 mmol/l). The same modification was carried out 12 weeks after the beginning active drug treatment with the same criteria. The baselines of total cholesterol were 3.24 +/- 0.69 g/l (8.38 +/- 1.78 mmol/l) 3.21 +/- 0.72 g/l (8.31 +/- 1.87 mmol/l) for patients with simvastatin and those with gemfibrozil respectively. So, at the end of active treatment, 64% of patients in the simvastatin group (n = 67) received 40 mg q.p.m. After 18 weeks of treatment, 89% of patients treated with Simvastatin and 37% with gemfibrozil had more than 20% reduction in LDL cholesterol. Simvastatin was more efficient on total cholesterol, LDL-C and apo B. The increase of HDL-C is similar in both groups of patients. In contrast, the level of triglycerides was further decreased by gemfibrozil. The tolerance was good in the two groups of patients and no difference in the frequency of side effects was observed.