Objective: To assess relationships between energy, nutrient and food intakes, alcohol consumption, smoking status and body mass index (BMI), and serum concentrations of b-carotene, a-tocopherol, vitamin C, selenium and zinc. Methods: Data on health status, alcohol consumption, smoking habits, anthropometric data and biochemical measurements were obtained in 1821 women aged 35-60 y and 1307 men aged 45-60 y, participant to the SU.VI.MAX Study. Data on dietary intake were available on a subsample who reported six 24-h dietary records during the first 18 months of the study. Results: Women had higher baseline serum b-carotene and vitamin C concentrations and lower concentration for serum vitamin E, zinc and selenium than men. In women, younger age was associated with lowered mean concentration of serum b-carotene, vitamin E and selenium. In men, only differences were observed for serum zinc, which was lower in older men. Current smokers of both sexes had significantly lower concentrations of serum b-carotene, vitamin C and selenium, and, only in women, of vitamin E, than nonsmokers. Alcohol consumers had lower concentrations of serum b-carotene and higher selenium concentrations. Serum b-carotene and vitamin C concentrations were lower in obese subjects. There were positive associations of dietary b-carotene, vitamin C and E with their serum concentrations. Age, nutrient and alcohol intakes, serum cholesterol, BMI and smoking status explained 15.2% of the variance of serum b-carotene in men and 13.9% in women, and 10.8 and 10.0% for serum vitamin C, and 26.3 and 28.6% for serum vitamin E, respectively. Conclusion: Serum antioxidant nutrient concentrations are primarily influenced by sex, age, obesity, tobacco smoking, alcohol consumption and especially dietary intake of those antioxidant nutrients. IntroductionCigarette smoking, obesity and some dietary patterns are well-known risk factors for both cardiovascular disease and cancer (WCRF/AIC; Kromhout, 2001). Yet, in the past several years, an increasing number of basic and clinical studies have pointed to the role of the reactive metabolites of oxygen, the free radicals, in these pathological processes, and the potential protective effect of antioxidant nutrients such as bcarotene, vitamin C, vitamin E, selenium and zinc (Ames, Halliwell & Gutteridge, 1989;Diplock, 1991;Byers & Perry, 1992;Frei, 1994;Hercberg et al, 1998a).Epidemiological data from cross-sectional, case-control, and prospective studies have shown a strong relationship between the intake of foods rich in antioxidant vitamins and minerals, or the actual intake of these nutrients, and the risk of cancer and ischaemic cardiovascular diseases (CVD) (Block et al, 1992;Stampfer & Rimm, 1993;Byers & Guerrero, 1995;Kohlmeier & Hastings, 1995;Stampfer & Rimm, 1995;Hercberg et al, 1998a). However, most of published randomized placebo-controlled primary prevention trials have not been able to demonstrate these potential beneficial effects (Blot et al, 1993; The AlphaTocopherol, Beta Carotene Cancer Preventi...

The link between vascular calcification (VC) and increased mortality is now well established. Over time, as clinical importance of this phenomenon has begun to be fully considered, scientists have highlighted more and more physiopathological mechanisms and signaling pathways that underlie VC. Several conditions such as diabetes, dyslipidemia and renal diseases are undoubtedly identified as predisposing factors. But even if the process is better understood, many questions still remain unanswered. This review briefly develops the various theories that attempt to explain mineralization genesis. Nonetheless, the main purpose of the article is to provide a profile of the various existing biomarkers of VC. Indeed, in the past years, a lot of inhibitors and promoters, which form a dense and interconnected network, were identified. Given importance to assess and control mineralization process, a focusing on accumulated knowledge of each marker seemed to be necessary. Therefore, we tried to define their respective role in the physiopathology and how they can contribute to calcification risk assessment. Among these, Klotho/fibroblast growth factor-23, fetuin-A, Matrix Gla protein, Bone morphogenetic protein-2, osteoprotegerin, osteopontin, osteonectin, osteocalcin, pyrophosphate and sclerostin are specifically discussed.

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Plasma selenium (Se), zinc (Zn) and copper (Cu) levels and antioxidant metalloenzymes, glutathione peroxidase (GPX) and superoxide dismutase (SOD), were studied in 17 patients on maintenance hemodialysis (HD) (group I), 14 uremic patients (group II) and 14 healthy subjects (group III). Plasma Se levels and erythrocyte GPX were significantly lower in the HD group (for Se: 0.69 ± 0.12 vs. 1.05 ± 0.13 μmol/l in controls; for erythrocyte GPX: 34.4 ± 6.4 vs. 49.2 ± 9 lU/g hemoglobin in controls) and a significant correlation was found between the two parameters (r = 0.66, p < 0.005). There was also a correlation between decreased plasma Zn and erythrocyte SOD activity (r = 0.58, p < 0.02) and between decreased plasma Cu and erythrocyte SOD (r = 0.60, p < 0.02). Plasma malondialdehyde levels were augmented in HD patients (5.08 ± 0.26 vs. 2.55 ± 0.15 μmol/l in controls and 2.79 ± 0.40 μmol/l in the uremic group). The catalase activity was increased in HD patients (202 ± 24 vs. 140 ± 40 IU/mg hemoglobin in group III). A defective antioxidant activity may thus contribute to increased peroxidative damage to cells in the course of dialysis.

The experimental finding of no beneficial effects of antioxidant supplementation in a generally well-nourished population is consistent with recent reports of a lack of efficacy of antioxidant supplements. However, the relations observed between the risk of MetS and baseline serum antioxidant concentrations, which probably reflect associations with overall dietary patterns, do support the current recommendations to consume antioxidant-rich foods. This trial was registered at clinicaltrials.gov as NCT00272428.

Background: Inadequate plasma selenium can adversely affect the maintenance of optimal health; therefore, reported decreases in plasma selenium in an aging population are cause for concern. To further examine this hypothesis, we explored the relationships between plasma selenium and mortality in an elderly population: the EVA (Etude du Vieillissement Artériel) study.

The effects of alcohol consumption on plasma concentrations of antioxidant vitamins (alpha-tocopherol and ascorbic acid), selenium, and markers of oxidative stress, especially malondialdehyde (MDA) and autoantibodies directed to MDA adducts to proteins (Ig-NH2-MDA) were investigated in a large population of 417 supposedly healthy men who consumed only low or moderate amounts of alcohol as compared with 102 alcoholic patients without severe liver disease, who were studied both before and after 21 d of withdrawal treatment. Plasma concentrations of alpha-tocopherol, ascorbic acid, and selenium were lower in alcoholics than in men who drank low amounts of alcohol (P < or = 0.001), whereas MDA and Ig-NH2-MDA were higher (P < or = 0.001). Plasma concentrations of alpha-tocopherol and selenium remained unchanged after the withdrawal period, whereas ascorbic acid (P < or = 0.01), MDA, and Ig-NH2-MDA concentrations decreased (P < or = 0.001). Adjustment of data for circulating lipids and nutritional intake suggests a specific effect of alcohol on antioxidant vitamins, independent of nutritional status.

IntroductionOccurrence of multiple brain metastases is a critical evolution of many cancers with significant neurological and overall survival consequences, despite new targeted therapy and standard whole brain radiotherapy (WBRT). A gadolinium-based nanoparticle, AGuIX, has recently demonstrated its effectiveness as theranostic and radiosensitiser agent in preclinical studies. The favourable toxicity profile in animals and its administration as a simple intravenous injection has motivated its use in patients with this first in human study.Methods and analysisThe NANO-RAD study is a phase I, first in human injection, monocentric, open-label, dose-escalation study to investigate the safety, the tolerability and the spectrum of side effects of AGuIX in combination with WBRT (30 Gy, 10 fractions of 3 Gy) for patients with multiple brain metastases. Five dose escalation cohorts are planned: 15, 30, 50, 75 and 100 mg/kg. A total of 15–18 patients will be recruited into this trial. The primary objective is to determine the maximum-tolerated dose of AGuIX nanoparticles combined with WBRT for the treatment of multiple brain metastases. Toxicity will be assessed using the National Cancer Institute Common Toxicity Criteria V.4.03. Secondary objectives are pharmacokinetic profile, distribution of AGuIX in metastases and surrounding healthy tissue visualised by MRI, intracranial progression-free survival and overall survival. Intracranial response will be determined according to Response Evaluation Criteria in Solid Tumour Criteria V.1.1 comparing MRI performed prior to treatment and at each follow-up visits.Ethics and disseminationApproval was obtained from the ethics committee Sud Est V, France (Reference number 15-CHUG-48). The study was approved by the French National Agency for the Safety of Medicines and Health Products (ANSM) (Reference number 151519A-12). The results will be published in peer-reviewed journals or disseminated through national and international conferences.Trial registration numberNCT02820454; Pre-results.