French Paradox Research Articles

The Patient Barrier to Growth of Bariatric Surgery: Another French Paradox?

The bariatric surgery community is complaining about the multiple barriers that hamper the growth of procedures that have been found to be the only effective treatment for morbid obesity. The French situation demonstrates that the number of procedures has stabilized after a period of rapid growth, despite the facts that the needs are not satisfied and that there are less important barriers to surgery than in most countries. This new "French paradox" is understandable if one accepts the reluctance of the public audience and an insufficient level of evidence for a systematic referral to bariatric surgery. Less invasive procedures should make it possible to re-unify the physicians who deal with obesity, as well as the implementation of comparatives and randomized clinical studies.

The French Paradox

The French Paradox

Umbilical cord blood banking: economic and therapeutic challenges

Since the first successful transplantation of umbilical cord blood in 1987, cord blood has become an important source of haematopoietic stem cells for the treatment of blood and genetic disorders. Important progress has been accompanied by challenges for scientists, ethicists and health policy-makers. With the increasing focus on cord blood as an alternative to human embryos and as a source of tissue for regenerative medicine, umbilical cord blood stem cells have attracted significant attention. In this paper, we review the therapeutic challenges and the competition between private and public cord blood banks, and also between cord blood inventories and bone marrow registries. We provide an international overview of banking activities, with a special focus on the French paradox. From access to bioresources to patent controversies, we analyse the economic impact of cord blood banking on health policies, and then discuss some ethical dilemmas of stem cell research.

Flavonoid-rich grapeseed extracts: a new approach in high cardiovascular risk patients?

The management of traditional risk factors such as hypertension and dyslipidaemia has been successful in reducing the development of cardiovascular disease. However, this has not resulted in the amelioration of complications; prompting attention to be focused on novel markers of vascular risk such as endothelial dysfunction (a determinant of vascular tone), vascular inflammation, oxidative stress and insulin resistance. With an ever-growing interest in plant-derived products, agents that could have a beneficial effect on this complex web of pathophysiology have thus been a major area of research and interest. Flavonoids have been a major focus of attention since the days of the French paradox and the presence of high quantity of flavonoids in grapeseed extracts has prompted research looking at its effects on novel markers of vascular risk. This review briefly summarises mechanisms implicated in the development of vascular disease and then focuses upon the potential role of the antioxidant properties of flavonoid-rich grapeseed extracts in the reversal of these processes.

Work/Family Policy in France: From State Familialism to State Feminism?

When one looks at the policies that target the relationship between work and family (here labelled 'work/family policies'), contradictory views come from France. On the one hand, the state recognition of family interests is very strong, and was initially rooted in familialism, an ideology that promotes the family as an institution, and has often played against women's rights. On the other hand, women's - and especially mothers' - labour force participation has always been relatively high compared to other western countries. To account for this 'French paradox', this paper puts work/family policies into historical perspective, in order to analyse them as a mix of policies coming from various public policy institutions (work, education, family). While state familialism has always been strong in France, it has been challenged and shattered by several social and political trends since the 1960s. Among these is the development of 'state feminism', with the creation of governmental bodies endowed with the formal mission of furthering women's rights. Based on an empirical study of these institutions, this paper shows how they reframed work/family policy in terms of a policy of equality in employment.

Alcohol and Hypertension

in which some of the key issues surrounding the topic were discussed. Compared with lifetime abstainers, those who reported drinking on a daily basis or apart from food had a significantly higher risk of hypertension, but this effect disappeared after accounting for the amount of alcohol consumed in the previous 30 days. When current drinkers only were studied and adjustment made for the amount of alcohol consumed in the previous 30 days, the risk of being hypertensive increased (64%) only in those who said they drank without food. Preference for any one type of beverage did not influence the association but the important potential confounder of dietary habits was not assessed. Nevertheless this finding was consistent with an earlier study of Italian wine drinkers coming from a different cultural background,4 and a follow-up in that population showed drinking alcohol outside of meals was associated with higher risk of death from all causes and cardiovascular disease. Similar relationships were seen between drinking outside of meals or snacks and increased risk of myocardial infarction in a recent case control study in men.5

Vascular dysfunction in aging: potential effects of resveratrol, an anti-inflammatory phytoestrogen.

Epidemiological studies demonstrated that even in the absence of other risk factors (e.g. diabetes, hypertension, hyperhomocysteinemia, hypercholesterolemia), advanced age itself significantly increases cardiovascular morbidity by enhancing vascular oxidative stress and inflammation. Because the population in the Western world is rapidly aging, there is a substantial need for pharmacological interventions that delay the functional decline of the cardiovascular system. Resveratrol is an atoxic phytoestrogen found in more than 70 plants including grapevine and berries. Recent data suggest that nutritional intake of resveratrol and other polyphenol compounds may contribute to the "French paradox", the unexpectedly low cardiovascular morbidity in the Mediterranean population. There is increasing evidence that resveratrol exerts multifaceted anti-oxidant and/or anti-inflammatory effects in various disease models. Importantly, resveratrol was reported to slow aging and increase lifespan in simple organisms and has been suggested as a potential calorie restriction mimetic. Resveratrol has also been reported to activate NAD-dependent histone deacetylases (sirtuins), which may contribute to its anti-aging effects. This review focuses on the role of oxidative stress and inflammation in cardiovascular dysfunction in aging, and on emerging anti-aging therapeutic strategies offered by resveratrol and other polyphenol compounds.

Internal and External Cues: French and American Explanations for Mindless Eating

Objective It is examined why the French, as compared to Americans, eat foods that have relatively higher fat content, yet have lower rates of cardiovascular disease and have lower body mass indices (also known as the French Paradox). Previous research suggests internal and external cues of eating behavior are thought to be indicative of French and American cultures respectively. Research Methods and Procedures A sample of 150 French and 152 American college age students were given a questionnaire that measured the influence of external and internal cues of meal cessation. All questions were rated on a nine-point scale with 1 indicating strong disagreement and 9 indicating strong agreement. Results In all cases, Americans were influenced more by external cues than internal cues. Specifically, more so than the French, Americans reported that they usually stopped eating when they thought others thought was normal, when everyone was finished, when they ran out of a beverage, when it was getting late, when their TV show was over, and when they were through with what they were reading. Conclusions External cues of meal cessation (i.e., finished eating when TV show is over or done reading) may lead to “mindless eating.” It seems that Americans may be particularly vulnerable to “mindless eating,” which could lead to obesity. Environments should be examined for their propensity to contribute to “mindless eating.” The French may be a model for “mindful eating,” which may lead to a more healthful relationship with food. Research supported by Cornell University’s Food and Brand Lab

Cytokine stimulation of pregnancy-associated plasma protein A expression in human coronary artery smooth muscle cells: inhibition by resveratrol

Through specific cleavage of proteins that bind and inhibit insulin-like growth factor-I (IGF-I), pregnancy-associated plasma protein-A (PAPP-A) enhances local IGF-I availability, and, consequently, receptor activation. PAPP-A expression is increased in experimental models of vascular injury and in human atherosclerotic plaque; however, little is known about the regulation of PAPP-A gene expression in vascular cells. In this study, we tested the hypothesis that proinflammatory cytokines involved in the vascular injury response stimulate PAPP-A gene expression in human coronary artery smooth muscle cells (hCASMC) in culture. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta stimulated PAPP-A gene expression in a time- and dose-dependent manner. The effect of these cytokines appears to be at the level of transcription because actinomycin D completely prevented the induction of PAPP-A gene expression. Accumulation of PAPP-A in cell-conditioned medium paralleled mRNA synthesis, as did proteolytic activity against IGF binding protein-4 (IGFBP-4). Interestingly, pretreatment of hCASMC with resveratrol, a polyphenol found in the skin of grapes and in red wine purported to underlie the "French paradox," inhibited TNF-alpha- and IL-1beta-induced PAPP-A expression and, hence, its IGFBP-4 proteolytic activity. Resveratrol had no effect on basal PAPP-A expression and protease activity. Our finding that PAPP-A gene expression in hCASMC is stimulated by TNF-alpha and IL-1beta suggests a mechanism for the regulation of PAPP-A in response to vascular injury that may contribute to the enhanced IGF-I bioactivity in intimal hyperplasia and atherosclerotic plaque development. Our results also suggest that PAPP-A may be a target of the cardiovascular system-protective effects of resveratrol.

Resveratrol inhibits vascular smooth muscle cell proliferation and induces apoptosis

In France, despite a high intake of dietary cholesterol and saturated fat, the cardiovascular death rate is one of the lowest among developed countries. This "French paradox" has been postulated to be related to the high red wine intake in France. The aim of this study was to determine the effects of resveratrol, a major polyphenol component of red wine, on vascular smooth muscle cell (SMC) proliferation in vitro. SMCs were exposed to 10(-6) to 10(-4) M resveratrol and cell proliferation was assessed by cell counting. Cell cycle analysis was done by treating cells with propidium iodide followed by flow-activated cell sorting. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining. We demonstrate that resveratrol inhibited bovine aortic SMC proliferation in a dose-dependent manner. The lowest concentration of resveratrol resulting in a significant decrease in SMC proliferation compared with control was 10(-5) M. By flow cytometry, we observed a block in the G1-S phase of the SMC cycle. Resveratrol treatment also resulted in a dose-dependent apoptosis of SMCs but had no effects on SMC morphology. The results indicated that vascular SMC proliferation could be inhibited by resveratrol through a block on G1-S phase and by an increase in apoptosis. It supports the conjecture that red wine consumption may have a beneficial effect on cardiovascular mortality. Our results suggest that resveratrol inhibits, in a dose-dependent manner, smooth muscle cell proliferation, which may help to partially explain a beneficial effect of wine drinking. This inhibition is related to an early block in the cell cycle and also to a dose-dependent apoptotic effect. The present study demonstrates that resveratrol not only is an indirect marker of a healthy life style and alimentation but may also be directly responsible for the French paradox.

NRH:quinone reductase 2: An enzyme of surprises and mysteries

Quinone reductase 2 has been discovered in 1961 and rediscovered in 1997. Because of its sequence homology with quinone reductase 1, it has been suspected to detoxify quinones. Ten years later, evidences begin to point to a versatile role of this enzyme. Indeed, QR2 is strongly suspected to be the molecular target of anti-malarian drugs such as chloroquin or paraquine, and of red wine-derived resveratrol that might be responsible for the so-called French paradox. It also is identical to the melatonin binding site MT 3, and might therefore be a rationale explanation for the antioxidant role of melatonin. Finally QR2 might be implicated in the toxicity, in vivo, of quinones such as menadione. The present commentary attempts to summarize this information and discusses a series of hypotheses.

ALCOHOL AND HYPERTENSION: AN OLD RELATIONSHIP REVISITED

( Received 4 May 2005; first review notified 11 July 2005; in revised form 20 September 2005; accepted 21 September 2005 ) The American comedian Henny Youngman (1906–1998) once said, ‘When I read about the evils of drinking, I gave up reading.’ Ironic, but interestingly as though with a sense of foresight, he did not speak of giving up drinking! It is despite the fact that alcohol is responsible for increased illness, being causally related to more than 60 different medical conditions (Rehm et al ., 2003). Around 4% of the global disease burden is also thought to be alcohol related, which is comparable with that attributed to the effects of tobacco (4.1%) and high blood pressure (4.4%) (Ezzati et al ., 2002; WHO, 2002). For most diseases related to alcohol consumption, a dose–response relationship exists with risk of the disease increasing with greater amounts of alcohol intake, with cardiovascular disease being a possible exception. Apart from being linked to disease, alcohol is also associated with violent crime and aggression under certain circumstances (Room and Rossow, 2001). The relationship between alcohol and cardiovascular disease, especially hypertension and coronary heart disease, is not as clear-cut. In France, the prevalence of coronary artery disease is lower—although their diets and their dietary fat content remain the similar—compared with many other Western countries. This was attributed to their tradition of wine drinking and these observations led to the so-called French paradox (Renaud and de Lorgeril, 1992) and an often-used excuse to enjoy a nice Bordeaux with every meal. However, both cross-sectional and prospective epidemiological studies …

Cardioprotective Effects of Dietary Polyphenols

Dietary polyphenols have been shown to possess cardioprotective effects. For example, the most noted role of grape polyphenols is in the French Paradox, in which a diet high in saturated fat accompanied by regular consumption of red wine is associated with a low risk of coronary heart disease (CHD). Initially, the paradox was thought to be driven by the postulated major action of grape polyphenols in inhibiting LDL oxidation. Although many studies have shown inhibitory effects of polyphenols on LDL oxidation, there have been an equal number of studies that showed a null effect on this variable. Although there are contrasting viewpoints on the effects of polyphenols on LDL oxidation variables, there is increasing evidence that these compounds possess additional cardioprotective functions including altering hepatic cholesterol absorption, triglyceride assembly and secretion, the processing of lipoproteins in plasma, and inflammation. It is the purpose of this review to examine recent information on the multiple functions of dietary polyphenols, with an emphasis on grape polyphenols, in decreasing the risk of CHD by improving plasma lipid profiles and reducing inflammation.

Antioxidant therapy: myth or reality?

New terms such as oxidative stress, antioxidant products or pro-oxidant risks are becoming familiar and an increasing number of international scientific conferences and the publication of thousands of scientific articles is an indication of the growing interest that the subject awakens. The most publicized example is perhaps the French paradox, based on the apparent compatibility of a high fat diet with a low incidence of coronary atherosclerosis attributed to the regular consumption, by the French, of red wine and/or grape juice. Flavonoids, and other phenolic substances contained in red wine, are assigned with antioxidant properties, which lower the oxidation of low density lipoproteins and consequently, the risk of atherogenic diseases. Other examples are the aging process and its correlation with an increase of free radicals, and the correlation between the initiation and promotion of cancer and tissue injury by free radicals, which has induced the intake of antioxidant products as chemical factors that prevent the onset of the disease. Currently, the incidence of oxidative stress on the onset and evolution of more than 100 diseases is claimed by several researchers. All these are realities, which on the other hand, are lacking of more clinical evidence, are considered by both physicians and health regulatory bodies, either as myths or of secondary importance. In the attempts to destroy those myths, results of chemical, pre-clinical, and clinical works with a crude extract of mango (Mangifera indica L.) stem bark, which has been developed in Cuba, are reviewed, with a strong experimental evidence of its antioxidant, anti-inflammatory and immunomodulatory properties.

Arthroplastie totale de hanche du sujet actif de moins de 50 ans

Introduction More than young age, high activity level is worldwide highlighted as the major factor affecting the longevity of primary total hip replacement (THR). Aim of this multicentric French symposium was to overview the results of current prosthetic options choosen by a pannel of members of the “Hip and Knee French Society“ (SFHG) to treat 1ary or 2ary hip arthritis in active and younger than 50 years old patients. Material and methods According to the selection criteria (ie., virgin or hardware-free hips, no high dysplasia > Crowe 2, no rheumatoïd or juvenile arthritis, activity > Devane 2 and age < 50), 1419 1ary THRs were reviewed, performed by 12 surgical groups from 17 institutions. The majority (72%) of the 9 implant combinations had cementless fixation (89% HA coated), 15.1% were fixed with cement and 10% had hybrid fixation. Mean age was 41.2 years and activity level graded Devane 4 and 5 was reported for 55.7% of patients (inter-series range, isr, 38 to 81%). Main diagnosis were hip osteonecrosis (36%) and dysplasia in 27%. Results At 7.9 year average follow-up (isr, 6.4 to 14.2 years), overall complication rate was 2.5% and average reoperation rate was 7.3% (isr, 3.8 to 13%). Ten-year survival rate from revision for any cause was > 95% for all THR combinations except for 3: the cementless Bousquet THR (86.4%, mainly due to failure of fixation of alumina coated double cup), the cementless ABG THR (90.9%, mainly due to acetabular osteolysis of HA-coated cup with zirconia-PE bearings) and the hybrid Osteal-Cerafit THR with alumina-alumina bearings (90.4%). With revision for aseptic loosening, 10-year survivorship was < 95% for 2 THR combinations: 88.6% for the Bousquet THR and 92.3% for the Osteal-Cerafit THR, whilst up to 100% for4 cementless combinations (the ABG-HA, the Omnifit-HA and the non-HA Alloclassic-Armor or CSF cups). With bearing revision (for wear, fracture, osteolysis and dislocation or impingement), 10-year survival was < 97% only for the Zirconia-PE (94%). Discussion and conclusion The main limits of the study were its retrospective aspect except for 3 series, an average follow-up < 10 years. Nevertheless, some observations can be drawn. 1/On the femoral side, cementing according to the “French paradox“ technique remained an efficient option, at least with smooth super-steel implant like the Charnley-Kerboull stem (10-year survival from revision for aseptic lossening, 97.6%); nevertheless, in this young and active population, all 6 uncemented stems showed better survival than the 2 smooth cemented ones. 2/On the acetabular side, except the alumina-coated Bousquet cup and the Ti-mesh Cerafit-cup, either cemented (Charnley-Kerboull) or all other cementless cups, including the threaded rings, provided 10-year survivorship > 99%. 3/At least, the 7.9 year average follow-up was not sufficient to show any significant difference between 10-year survival of the various bearings used, including hard-on-hard ones (alumina-alumina 32 mm, 98.6% survival at 10 years; Metasul 28 mm, 100% survival but at 8 years only). Another decade will be necessary to allow more conclusive appraisal on this crucial matter.

Quercetin-Induced Induction of the NO/cGMP Pathway Depends on Ca2+-Activated K+Channel-Induced Hyperpolarization-Mediated Ca2+-Entry into Cultured Human Endothelial Cells

Quercetin is one of the dietary-derived flavonoids that are held responsible for the beneficial effects of red wine drinking in coronary artery disease known as the "French paradox". We examined whether quercetin modulates endothelial function by influencing Ca2+-activated K+ channels with large conductance (BK(Ca)) in cultured human endothelial cells. Membrane potential and intracellular Ca2+ concentrations of cultured human endothelial cells derived from umbilical cord veins (HUVEC) were measured using the fluorescence dyes DiBAC, and FURA-2, respectively. NO production was examined using a cGMP radioimmunoassay. HUVEC proliferation was analyzed by cell counts and thymidine incorporation. A dose-dependent hyperpolarization of HUVEC was recorded when quercetin was added (5-100 micromol/L). The maximum effect (50 micromol/L) was significantly reduced by the addition of the highly selective BK(Ca) inhibitor iberiotoxin (100 nmol/L), but not by blockers of other Ca2+-activated K+ channels (n = 30; p < 0.05). This BK(Ca)-induced hyperpolarization caused a transmembrane Ca2+ influx, because the quercetin-induced increase of intracellular Ca2+ was blocked by iberiotoxin, or by applying 2-aminoethoxydiphenylborate (100 micromol/L)--an inhibitor of capacitative Ca2+ entry (n = 30; p < 0.05). Quercetin-induced cGMP levels were significantly reduced by the eNOS-inhibitor l-NMMA (300 micromol/L), and by iberiotoxin (n = 10; p < 0.05). Endothelial proliferation was significantly reduced by 56 % when cells were incubated with quercetin (n = 12; p < 0.05). This effect was due to the increased NO production, because it was reversed when the cells were treated with a combination of quercetin and l-NMMA. In conclusion quercetin improves endothelial dysfunction by increasing NO synthesis involving BK(Ca)-dependent membrane hyperpolarization-induced capacitative Ca 2+ entry. Increased NO production is responsible for the quercetin-dependent inhibition of endothelial proliferation.

Bacchic Medicine: Wine and Alcohol Therapies from Napoleon to the French Paradox (review)

Bacchic Medicine: Wine and Alcohol Therapies from Napoleon to the French Paradox (review)

The effect of resveratrol on cholecystokinin-octapeptide-induced experimental pancreatitis in rats

Resveratrol is a phytoalexin that reaches high concentrations in the skin of grapes and in red wine. The antioxidant, anti-inflammatory and also anti-cancer effects of the substance were shown in several in vivo and in vitro experiments. Moreover, this dietary component is thought to be responsible for the so-called “French paradox“, describing the association of red wine consumption and reduced mortality of breast cancer and coronary heart disease.

Vascular Effects of Alcoholic Beverages

The relationship between alcoholic beverage consumption and cardiovascular disease is complex and not fully elucidated. The idea that drinking moderately protects against coronary heart disease prevails among physicians and the public at large. There are 218 reviews in MedLine under the search terms “coronary heart disease alcohol,” limited to title and abstract, almost all asserting that the consumption of moderate amounts of alcoholic beverages is beneficial for cardiovascular health. Wine is the beverage typically associated with cardioprotection, being presumably a determinant of the low incidence of CHD in France, the French paradox. The epidemiological evidence comes along with the demonstration of beneficial effects of alcohol or other wine products on some mediators of cardiovascular disease, such as blood lipoproteins, clotting and fibrinolytic factors, insulin sensitivity, endothelin, NO, and LDL susceptibility to oxidation. However, not all epidemiological studies have shown a cardiovascular protection derived from the moderate consumption of alcoholic beverages. In blacks, this amount of consumption was associated with an increased risk for coronary heart disease incidence.1 The observational design of studies that have demonstrated the beneficial effect of alcoholic beverages precluded the full control of confounding by a healthier lifestyle of moderate drinkers. In addition, other negative cardiovascular effects of alcohol could nullify …

Molecular mechanisms of the chemopreventive effects of resveratrol and its analogs in carcinogenesis

Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to exhibit a wide range of biological and pharmacological properties. It has been speculated that dietary resveratrol could be an explanation for the so-called 'French paradox' as it may act as an antioxidant, promote nitric oxide production, inhibit platelet aggregation, and increase high-density lipoprotein cholesterol, and thereby serve as a cardioprotective agent. Recently, it has been demonstrated that resveratrol can function as a cancer chemopreventive agent, and there has been a great deal of experimental effort directed toward defining this effect. It has been shown that resveratrol and some of its analogs interfere with signal transduction pathways, modulate cell cycle-regulating proteins, and is a potent inducer of apoptosis in multiple carcinoma cell lines. This review summarizes the recent advances that have provided new insights into the molecular mechanisms underlying the promising properties of resveratrol.