French Paradox Research Articles

Resveratrol in the treatment of asthma based on an animal model.

Resveratrol is a natural polyphenol found, for example, in red wine, grapes or nuts. One of the resveratrol’s health properties is a cardioprotective activity – it is believed that resveratrol is responsible for the French paradox and anticancer activity. Moreover, the effectiveness of resveratrol in the treatment of asthma is confirmed by multiple research. Resveratrol displays a multiway impact on the reduction of the symptoms of the disease which contributes to the alleviation of inflammation i.a. by: inhibition of cellular infiltration, suppression of oxidative stress, reduction in the volume of mucus, relaxation of smooth muscle, stalling of the fibrosis affecting the respiratory tract or counteracting bronchial hyperresponsiveness. Resveratrol reduces the concentration of eosinophils, pro-inflammatory interleukins and interferes with many signal transduction pathways. In case of concomitance of obesity, resveratrol alleviates the course of asthma. The review juxtaposes the mechanisms of resveratrol activity and presents the results of the published research conducted on rodents.

Is the French Paradox cementing philosophy superior to the standard cementing? A randomized controlled radiostereometric trial and comparative analysis.

AimsHighly polished stems with force-closed design have shown satisfactory clinical results despite being related to relatively high early migration. It has been suggested that the minimal thickness of cement mantles surrounding the femoral stem should be 2 mm to 4 mm to avoid aseptic loosening. The line-to-line cementing technique of the femoral stem, designed to achieve stem press-fit, challenges this opinion. We compared the migration of a highly polished stem with force-closed design by standard and line-to-line cementing to investigate whether differences in early migration of the stems occur in a clinical study.MethodsIn this single-blind, randomized controlled, clinical radiostereometric analysis (RSA) study, the migration pattern of the cemented Corail hip stem was compared between line-to-line and standard cementing in 48 arthroplasties. The primary outcome measure was femoral stem migration in terms of rotation and translation around and along with the X-, Y-, and Z- axes measured using model-based RSA at three, 12, and 24 months. A linear mixed-effects model was used for statistical analysis.ResultsResults from mixed model analyses revealed a lower mean retroversion for line-to-line (0.72° (95% confidence interval (CI) 0.38° to 1.07°; p < 0.001), but no significant differences in subsidence between the techniques (-0.15 mm (95% CI -0.53 to 0.227; p = 0.429) at 24 months. Radiolucent lines measuring < 2 mm wide were found in three and five arthroplasties cemented by the standard and line-to-line method, respectively.ConclusionThe cemented Corail stem with a force-closed design seems to settle earlier and better with the line-to-line cementing method, although for subsidence the difference was not significant. However, the lower rate of migration into retroversion may reduce the wear and cement deformation, contributing to good long-term fixation and implant survival.Cite this article: Bone Joint J 2022;104-B(1):19–26.

Holiday heart syndrome: influence of alcohol on heart rhythm

The impact of alcohol on human health is widely known. There is a large body of research about positive (the “French paradox”) and negative effects of alcohol consumption. The relationship between excessive alcohol consumption and cardiac arrhythmias was first described in the 1970s in people who consumed alcohol heavily, mainly on weekends or holidays, but also in those who drank little or did not consume any alcohol. The term “holiday heart syndrome” was used for the first time by Philip Ettinger with reference to healthy people without cardiovascular disease. Excessive alcohol consumption can cause arrhythmias, most often in the form of atrial fibrillation. Ethanol and its metabolites have a toxic impact on cardiac myocytes; moreover, alcoholic cardiomyopathy accounts for one-third of all cases of non‐ischaemic dilated cardiomyopathy. It is possible to restore normal heart function through early diagnosis and cessation of alcohol consumption. The prevalence of holiday heart syndrome depends on the drinking habits of the study population. Holiday heart syndrome should be considered especially in patients without overt heart disease with a new onset of atrial fibrillation. Although relapses do occur, the clinical course is mild and specific antiarrhythmic therapy is usually not warranted. People diagnosed with cardiovascular disease benefit from minimising the amount of alcohol consumption. There is no safe amount of alcohol to drink and especially those with alcoholic cardiomyopathy should strive for abstinence in order to optimise treatment.

Based on Multi-Activity Integrated Strategy to Screening, Characterization and Quantification of Bioactive Compounds from Red Wine.

According to French Paradox, red wine was famous for the potential effects on coronary heart disease (CHD), but the specific compounds against CHD were unclear. Therefore, screening and characterization of bioactive compounds from red wine was extremely necessary. In this paper, the multi-activity integrated strategy was developed and validated to screen, identify and quantify active compounds from red wine by using ultra high performance liquid chromatography-fraction collector (UHPLC-FC), ultra fast liquid chromatography-quadrupole-time-of-flight/mass spectrometry (UFLC-Q-TOF/MS) and bioactive analysis. UHPLC-FC was employed to separate and collect the components from red wine, which was further identified by UFLC-Q-TOF/MS to acquire their structural information. Furthermore, the active fractions were tested for antioxidant activity, inhibitory activity against thrombin and lipase activities in vitro by the activity screening kit. As the results, there were 37 fractions had antioxidant activity, 22 fractions had thrombin inhibitory activity and 28 fractions had lipase inhibitory activity. Finally, 77 active components from red wine were screened and 12 ingredients out of them were selected for quantification based on the integration of multi-activity. Collectively, the multi-activity integrated strategy was helpful for the rapid and effective discovery of bioactive components, which provided reference for exploring the health care function of food.

French Paradox, Alcohol, and Health Related Concerns

French Paradox, Alcohol, and Health Related Concerns

Ex vivo to in vivo extrapolation of syringic acid and ferulic acid as grape juice proxies for endothelium-dependent vasodilation: Redefining vasoprotective resveratrol of the French paradox

Resveratrol, in wines, has been implicated to be primarily responsible for the French paradox, remaining controversial. Herein, we elucidated the representative vasodilation-increasing polyphenols from concord grape juice (CGJ) using ex vivo-to-in vivo extrapolation (EVIVE). We verified the interference-free antioxidant response of CGJ post-dose supernatant of deproteinated serum (CPSDS, as ex vivo proxy) in isolated aortic rings, and in healthy, and H2O2-treated endothelial cells (H-ECs). Syringic acid and ferulic acid (SF) were detected in CGJ and post-dose rat serum (PRS). In isolated aortic rings and H-ECs, polyphenols alone, or in combination, at doses equivalent to those detected in PRS, quantitatively reflected endothelium-dependent vasodilation of CPSDS, as evidenced by nitric oxide (NO) formation-mediated antioxidation-sensitive activation of Src kinase with subsequent PI3/Akt-dependent phosphorylation of endothelial NO synthase. Using EVIVE, SF closely reflected CGJ in coronary flow-mediated vasodilation. Hence, SF application in precision ethnomedicine may redefine antioxidant-sensitive vasoprotective resveratrol of the French paradox.

Wine Polyphenols and Health: Quantitative Research Literature Analysis

The relationship between wine polyphenols and health has been receiving growing scientific attention in the last few years. To confirm this point, the proposed paper identifies the major contributors to academic journals regarding the relationships between wine polyphenols and health. The endpoints of the proposed study are to provide a comprehensive overview and analysis of the literature regarding the relationships between wine polyphenol and health based on a bibliometric analysis. Bibliometric data were extracted from the Scopus online database using the search string TITLE-ABS-KEY (wine AND polyphenol* AND health OR (“french paradox” OR “cardiovascular disease*” OR atherosclerosis OR microbiota) and analyzed using the VOSviewer bibliometric software to generate bubble maps and to visualize the obtained results. This perspective paper analyzes: (i) the research themes addressing the relationships between wine polyphenols and health; (ii) the major contributors’ origin, e.g., country and/or regions; (iii) the institutions where the research is based; (iv) the authors; and (v) the type of paper. These results represent a useful tool to identify emerging research directions, collaboration networks, and suggestions for more in-depth literature searches.

Outcomes of Cemented Distal Femoral Replacement Using “Line to Line” Technique With All-Polyethylene Tibial Implant for Tumors

BackgroundBoth cemented and cementless stemmed endoprosthetic implants have been used to reconstruct large skeletal defects after tumor resection with similar outcomes. In this study, we examined the oncologic, clinical, and functional outcomes in patients undergoing distal femur replacement using the French paradox technique. MethodsA total of 125 patients who underwent distal femur replacement between 1990 and 2019 using the line-to-line cementation technique were reviewed. Implant failure was recorded as per Henderson’s classification. Functional outcomes were analyzed using the Musculoskeletal Tumor Society and Toronto Extremity Salvage Score scoring systems. The mean follow-up was 84 (1-350) months. ResultsAseptic loosening of the femoral stem was recorded in one patient at 21-years of follow-up. Twenty of 125 patients required bushing exchange for polyethylene wear, all after 10 years. Six tibial bearing component fractures were recorded in four patients while one femoral stem component Morse taper fractured. Two all-polyethylene cemented tibial implants were revised for polyethylene granuloma. Deep surgical site infection occurred in 13 patients, while six patients experienced local recurrence. Kaplan-Meier estimates for implant survival for all-cause revision were 85% at 1 year and 70% at 5 years. These estimates for femur or tibia loosening as an end point were 96% at 10 years and 90% at 15 years. The mean Musculoskeletal Tumor Society and Toronto Extremity Salvage Score scores at the last follow-up were 76% and 74%, respectively. Thirty-five patients died of disease progression. ConclusionThe line-to-line cementation technique, used with all-polyethylene tibial implants, demonstrates low incidence of aseptic loosening at medium and long-term follow-ups. Level of EvidenceIII.

The French paradox: Was it attributed to cheese consumption?

The French paradox: Was it attributed to cheese consumption?

Technological and nutritional aspects of milk chocolate enriched with grape pomace products

The French paradox is the observation of low heart disease death rates despite high intake of cholesterol and saturated fat, possibly related to the consumption of red wine containing polyphenols. Those are also found in pomace and affect health as radical catchers inhibiting cancer, inflammations and arteriosclerosis. European cocoa regulation allows incorporating up to 40% of added foodstuffs into chocolate, so grape pomace can be used. Cocoa itself is known as a very good source of phenolic compounds, and consequently dark chocolate is considered to have similar health benefits as red wine. Milk chocolates contain only little fat-free cocoa dry matter; therefore, grape pomace is considered most beneficial here. Entire pomace or flour from seeds have been tested to evaluate technical aspects as well as the impact on chocolate properties like particle size distribution, flow properties, total phenol content, antioxidative capacity and sensory perception. Initial trials revealed that additional drying and also pre-grinding was necessary before pomace can be used as an ingredient. Various samples were produced by the coarse conching process, which uses a ball mill for size reduction below 30 µm. A difficulty arises when some tough particles slip through without being properly ground; D99-values can be used to better control this issue. Grape pomace contains almost as many polyphenols as cocoa liquor, so it can serve as a substitute. Its content and thus quality depends on gentle drying. Finally, adding, e.g., just 3.5% was able to significantly increase the polyphenol contents of milk chocolate.

The Development of Maillard Reaction, and Advanced Glycation End Product (AGE)-Receptor for AGE (RAGE) Signaling Inhibitors as Novel Therapeutic Strategies for Patients with AGE-Related Diseases.

Advanced glycation end products (AGEs) are generated by nonenzymatic modifications of macromolecules (proteins, lipids, and nucleic acids) by saccharides (glucose, fructose, and pentose) via Maillard reaction. The formed AGE molecules can be catabolized and cleared by glyoxalase I and II in renal proximal tubular cells. AGE-related diseases include physiological aging, neurodegenerative/neuroinflammatory diseases, diabetes mellitus (DM) and its complications, autoimmune/rheumatic inflammatory diseases, bone-degenerative diseases, and chronic renal diseases. AGEs, by binding to receptors for AGE (RAGEs), alter innate and adaptive immune responses to induce inflammation and immunosuppression via the generation of proinflammatory cytokines, reactive oxygen species (ROS), and reactive nitrogen intermediates (RNI). These pathological molecules cause vascular endothelial/smooth muscular/connective tissue-cell and renal mesangial/endothelial/podocytic-cell damage in AGE-related diseases. In the present review, we first focus on the cellular and molecular bases of AGE–RAGE axis signaling pathways in AGE-related diseases. Then, we discuss in detail the modes of action of newly discovered novel biomolecules and phytochemical compounds, such as Maillard reaction and AGE–RAGE signaling inhibitors. These molecules are expected to become the new therapeutic strategies for patients with AGE-related diseases in addition to the traditional hypoglycemic and anti-hypertensive agents. We particularly emphasize the importance of “metabolic memory”, the “French paradox”, and the pharmacokinetics and therapeutic dosing of the effective natural compounds associated with pharmacogenetics in the treatment of AGE-related diseases. Lastly, we propose prospective investigations for solving the enigmas in AGE-mediated pathological effects.

Are all wines made from various grape varieties beneficial in the prevention of myocardial infarction and stroke?

Aim:Epidemiologic studies support the assumption (French paradox hypothesis) that drinking red wine is beneficial in the prevention of cardiovascular diseases. Our recent works however cast doubt on such claim. Earlier we have shown that the antithrombotic activity of various fruits and vegetables mainly depends on their varieties. For this reason, several varieties of red and white grapes were tested for antithrombotic effect in animal experiments.Results:Antithrombotic effect of 45 red and white grape varieties were assessed in the present study. Out of the 45, one red grape variety showed antithrombotic effect, while the majority of red and white grape varieties enhanced thrombosis.Conclusion:Most red and white grape varieties enhanced thrombotic activity of blood.

Механізми кардіо- та вазопротекторної дії ресвератролу

У статті наведено огляд сучасних даних щодо механізмів реалізації кардіо- та вазопротекторної дії ресвератролу. Наведені результати експериментальних і клінічних досліджень, що підтверджують можливість включення ресвератролу в фармакотерапію серцево-судинних захворювань. Вплив ресвератролу на серцево-судинну систему полягає в підвищенні продукції NO, зниженні синтезу ендотеліну-1, проявів оксидативного стресу, запобіганні проліферації клітин гладеньких м’язів, ремоделюванні судин та посиленні жорсткості артерій. Крім того, ресвератрол знижує інфільтрацію імунних клітин у судинну стінку та зменшує запалення судинної стінки. Ресвератрол має значну біологічну активність та може застосовуватися не тільки як кардіопротекторний, але й як протизапальний, антидіабетичний, нейротропний, протипухлинний засіб.

Short vs Standard-Length Femoral Stems Cemented According to the “French Paradox”: A Matched Paired Prospective Study Using Ein Bild Roentgen Analyze Femoral Component at Two-Year Follow-Up

BackgroundThe purpose of this prospective matched paired study is to compare the in vivo migration patterns using Ein Bild Roentgen Analyze femoral component of shortened vs standard-length stems cemented line-to-line in primary total hip arthroplasty (THA) at 2-year follow-up. MethodsWe prospectively included the first 50 consecutive primary cemented THAs in 50 patients using a 12% shortened stem (AmisK group) of which design was derived from the original Charnley-Kerboull (CK) femoral components. These 50 patients were matched paired to 50 patients from a historical series of patients who underwent primary THAs using standard-length CK stems (CK group) with available long-term results, including Ein Bild Roentgen Analyze femoral component data at 2-year follow-up. ResultsBody mass index was significantly higher (P = .007) in the AmisK vs the CK group. At the 2-year follow-up, the mean subsidence was 0.65 mm (0-1.40) in the AmisK group vs 0.68 mm (0.07-1.43) in the CK group (P = .73). When using a 1.5-mm threshold, none of the stems in either group was considered to have subsided. Femoral cortical thickening in zones 3 and 5 occurred in 6 of the 50 hips (12%) in the AmisK group vs 20 (40%) of the 50 hips in the CK group (P = .003). ConclusionOur study showed that a shortened highly polished double-tapered stem cemented line-to-line provided similar results including minimal subsidence as its standard-length counterpart, with significantly less distal femoral cortical thickening. However, longer term survival analysis still needs to be determined.

Does the line-to-line cementing technique of the femoral stem create an adequate cement mantle?

Background:The line-to-line cementing technique is proposed to create a press-fit in the femoral canal, which is contrary to modern cementing techniques. The term ‘French paradox’ has been used to describe the acceptable results associated with this technique. It has been suggested that the quality of the mantle may not be satisfactory, predisposing to early failure and aseptic loosening.Methods:The line-to-line cementing technique, where the femoral stem was oversized by 1 size compared to the broach, was compared to the standard cementing technique using corresponding sized broaches and stems, in 6 pairs of human cadaver femora with taper-slip design C-stems. Cement pressure was measured, and cement mantle thickness was analysed. A mixed effects model with random intercepts was used to examine the relationship between thickness of mantle and cementing technique and between pressure and cementing technique.Results:Line-to-line cementing results in significantly higher pressurisation for longer periods of time leading to better interdigitation but a thinner mantle in some areas.Conclusions:The results of this study describe the in-vitro advantages and disadvantages of the line-to-line cementing technique.

Fibrinogen Increases Resveratrol Solubility and Prevents it from Oxidation.

The French paradox describes a lower incidence of cardiovascular problems despite a high intake of saturated fats. This phenomenon was associated with higher consumption of red wine, as it was later discovered that the presence of antioxidants, including resveratrol, have beneficial effects. We hypothesized that resveratrol may have a more direct role in protection from harmful oxidation, presumably through binding to important proteins of the blood coagulation process. Spectrofluorimetry demonstrated that resveratrol is capable of binding to fibrinogen, the main protein in the coagulation process, which is also important as a food additive. Various spectroscopic methods determined that binding does not cause fibrinogen unfolding or destabilization since protein melting temperature remains unchanged. A mutually protective effect against the free radical-induced oxidation of polyphenol and fibrinogen was found. The presence of fibrinogen caused only a negligible masking effect of the antioxidative abilities of resveratrol, measured by a reduction of hexacyanoferrate (III), while greatly increasing its solubility in an aqueous environment, thus increasing its potential bioavailability. Due to its interaction with fibrinogen, resveratrol may serve as an antioxidant at the site of injury. The antioxidative effect of resveratrol may also protect and thus keep the desired characteristics of fibrinogen during the application of this protein as a food additive.

Radiographic, Functional, and Oncologic Outcomes of Cemented Modular Proximal Femur Replacement Using the “French Paradox” Technique

BackgroundEndoprostheses are frequently used in the management of tumors involving the proximal femur. Aseptic loosening is a common complication that has been linked to the cementing technique. The “French paradox” is well-known cementing technique in the arthroplasty literature. No previous reports have assessed loosening in proximal femur replacements using this technique. We examined rates of femoral stem aseptic loosening in proximal femur replacements, functional outcomes, complications, and oncologic outcomes. MethodsWe conducted a retrospective review of 47 patients who underwent proximal femur replacement between 2000 and 2019. Two reviewers evaluated preoperative and postoperative radiographs using the International Society of Limb Salvage scoring system and Barrack criteria for stem loosening. The acetabulum was evaluated according to the criteria of Baker et al. Functional outcomes were assessed using Musculoskeletal Tumor Society (MSTS) score and Toronto Extremity Salvage Score. The mean follow-up was 44 months. ResultsThe mean International Society of Limb Salvage scores for the 2 reviewers were 86% ± 6% and 84% ± 6%. The first reviewer graded femoral stem loosening as “possibly loose” in 2 patients, one of whom was graded as possibly loose by the second reviewer. The 2 reviewers found no acetabular erosion in 16 (70%) and 15 (65.4%) patients, respectively. The mean Musculoskeletal Tumor Society score and Toronto Extremity Salvage Score at last follow-up were 61% and 72%, respectively. Twenty complications occurred in 13 patients, and 5 patients experienced local recurrence. ConclusionDespite complications, we showed favorable femoral component survival rates. Cementing the proximal femur prosthesis with tight canal fit and thin cement mantle is a viable option for the short and medium term. Level of EvidenceIII.

Fluorescent Imaging of Resveratrol Induced Subcellular Cysteine Up-Regulation.

Even through many physiological pathways of resveratrol have been established since its association with the "French paradox" in 1992, its exact pathological roles are still ambiguous and disputable. To understand how resveratrol exerts its effects would not only enlighten the pathogenesis study of related diseases, but also promote the development of more potent molecules. Focusing on the reported cellular directly and indirectly ROS scavenging processes of resveratrol, we evaluated the activation effect of the inherent antioxidation thiols system in subcellular level by two cysteine (Cys) specific fluorescent probes mitochondria targetable Mito-1 and lysosomes targetable Ly-1. We found that 50 μM resveratrol treatment could induce distinct Cys up-regulation in both mitochondria and lysosomes which might be a general biological phenomenon in various cell lines for the first time.

The Microbiota-Gut-Brain Axis-Heart Shunt Part II: Prosaic Foods and the Brain-Heart Connection in Alzheimer Disease.

There is a strong cerebrovascular component to brain aging, Alzheimer disease, and vascular dementia. Foods, common drugs, and the polyphenolic compounds contained in wine modulate health both directly and through the gut microbiota. This observation and novel findings centered on nutrition, biochemistry, and metabolism, as well as the newer insights we gain into the microbiota-gut-brain axis, now lead us to propose a shunt to this classic triad, which involves the heart and cerebrovascular systems. The French paradox and prosaic foods, as they relate to the microbiota-gut-brain axis and neurodegenerative diseases, are discussed in this manuscript, which is the second part of a two-part series of concept papers addressing the notion that the microbiota and host liver metabolism all play roles in brain and heart health.

The Microbiota-Gut-Brain Axis Heart Shunt Part I: The French Paradox, Heart Disease and the Microbiota.

It has been well established that a vegetarian and polyphenol-rich diet, including fruits, vegetables, teas, juices, wine, indigestible fiber and whole grains, provide health-promoting phytochemicals and phytonutrients that are beneficial for the heart and brain. What is not well-characterized is the affect these foods have when co-metabolized within our dynamic gut and its colonizing flora. The concept of a heart shunt within the microbiota-gut-brain axis underscores the close association between brain and heart health and the so-called “French paradox” offers clues for understanding neurodegenerative and cerebrovascular diseases. Moreover, oxidation-redox reactions and redox properties of so-called brain and heart-protective foods are underappreciated as to their enhanced or deleterious mechanisms of action. Focusing on prodromal stages, and common mechanisms underlying heart, cerebrovascular and neurodegenerative diseases, we may unmask and understanding the means to better treat these related diseases.