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International audience; Designer benzodiazepines (DBZDs) have become of particular importance in the past few years. The metabolite monitoring of DBZD in biological fluids could be of great interest in clinical and forensic toxicology. However, DBZD metabolites are not known or not commercially available. The identification of some DBZD metabolites has been mostly explored by self-administration studies or by in vitro studies followed by high-resolution mass spectrometry. The question arose whether a unit resolution instrument could be efficient enough to allow the identification of DBZD metabolites. In this study, we used an in vitro experiment where eight DBZDs (diclazepam, flubromazepam, etizolam, deschloroetizolam, flubromazolam, nifoxipam, meclonazepam and clonazolam) were incubated with human liver microsomes (HLMs) and metabolite identification was carried out by using a UHPLC coupled to a QTRAP triple quadrupole linear iontrap tandem mass spectrometer system. Post-mortem samples obtained from a real poisoning case, involving deschloroetizolam and diclazepam, were also analysed and discussed. Our study using HLM allowed the identification of 26 metabolites of the 8 DBZDs. These were denitro-, mono- or di-hydroxylated and desmethyl metabolites. In the forensic case, diclazepam was not detected whereas its metabolites (lormetazepam and lorazepam) were present at high concentrations in urine. We also identified hydroxy-deschloroetizolam in urine, while the parent compound was not detected in this matrix. This supports the approach that LC coupled to a simple QTRAP could be used by laboratories to identify other not-known/not-commercialized new psychoactive substance (NPS) metabolites.

The effects of spirulina and its chromophore phycocyanin, both without bound Se or selenium-enriched, were studied on plasma cholesterol, early atherosclerosis, cardiac production of superoxide anions, and NAD(P)H oxidase expression in hamsters. Forty hamsters were divided into 5 groups of 8 and fed an atherogenic diet for 12 weeks. They received by gavage either 7.14 mL/(kg day) phycocyanin (PC), Se-rich phycocyanin (SePC), spirulina (SP) or Se-rich spirulina (SeSP) in water, or water as control. SeSP and SePC supplied 0.4 microg of Se per 100 g body weight. Plasma cholesterol and non-HDL cholesterol concentrations were lower in group consuming SePC. HDL-cholesterol was never affected. SePC significantly increased plasma antioxidant capacity by 42% compared with controls. A sparing effect in liver glutathione peroxidase (87% on average) and superoxide dismutase (56% on average) activity was observed for all the groups compared to controls. Aortic fatty streak area was significantly reduced in the experimental groups, especially by PC (82%) and SePC (85%). Cardiac production of superoxide anion significantly decreased by approximately 46-76% in the four experimental groups and especially in SePC group (76%). The expression of p22phox subunit of NAD(P)H oxidase decreased by 34% after consumption of SePC. The results indicate that chronic consumption of Se-rich spirulina phycocyanin powerfully prevents the development of atherosclerosis. The underlying mechanism is related mainly to inhibiting pro-oxidant factors and at a lesser extent improving the serum lipid profile.

Purpose To determine the association of potential risk factors, including antioxidant enzymes, with the incidence of cataract. Design Cohort study. Participants At baseline, the Age-Related Eye Diseases (Pathologies Oculaires Liees a l'Âge, POLA) Study included 2584 residents of Sete (southern France) aged 60 years or older. From September 1998 to May 2000, a 3-year follow-up examination was performed on 1947 of the 2436 surviving participants (79.9%). Methods Cataract classification was based on a standardized lens examination at the slit lamp, according to Lens Opacities Classification System III. Biologic measurements were performed at baseline from fasting blood samples. Main outcome measures At baseline and follow-up, the presence of cataract was defined as: NC or nuclear opalescence (NO) ≥ 4 for nuclear cataract, C≥4 for cortical cataract, and P≥2 for posterior cataract (PSC) opacities, using opacity grades corrected for interobserver variability. Incidence rates were assessed separately for right and left eyes and for each type of cataract. Results In the multivariate model, the incidence of cortical cataract was increased in subjects with high red blood cell superoxide dismutase activity (odds ratio [OR] 4.2 [1.5–12.1], P = 0.007). The incidence of PSC cataract was increased in subjects with a high level of plasma glutathione peroxidase (OR 1.8 [1.0–3.3], P = 0.05). In addition to age, gender, and opacities at baseline, significant risk factors for incident cataract were: long-duration diabetes (OR 5.8, P = 0.001 for cortical cataract) and lifetime heavy smoking (OR 2.9, P = 0.006 for PSC cataract). Conclusions Consistent with the baseline analysis, the results of this prospective study suggest that antioxidant enzymes might be implicated in the etiology of cataract.

Background: Our study investigated the biochemical and anthropometric characteristics in elite athletes of rugby union based in the south of France during the different periods of the competition to identify metabolic and biochemical adaptations to particular lifestyle conditions. Methods: Participants included 35 players in 2008 and 43 players in 2009. Biochemical variables [creatinine, uric acid, creatine kinase (CK), alanine aminotransferase, aspartate aminotransferase, C-reactive protein] were evaluated. Specifi c protein levels (albumin, acid α -glycoprotein, prealbumin), vitamins (A, E, C), antioxidant enzymes [glutathione peroxidase (GPx), superoxide dismutase (SOD)], oligoelements (Zn, Se, Cu, erythrocyte magnesium), homocysteine (Hcy), carnitine and the distribution of amino acids were specifi cally determined for our study during a pre-competition period (September 2008 and 2009). Results: Globally, no defi cit was observed for vitamins, oligonutrients and amino acids levels. The high SOD and GPx activities in rugby players suggest a presence of oxidative stress of exercise. The evaluation of renal function should be used with caution because of the interaction between creatinine and lean body mass. In addition, a profound effect of intense exercise on the CK values was reported to establish specifi c reference values for athletes. The analysis of the biological variation allows optimization of the interpretation of the changes from an increased or decreased baseline value from a season to the other one. Conclusions: The conclusions of present study were: 1) the necessity of rugby-specifi c reference intervals for CK and creatinine parameters; 2) the use of enzymatic creatinine for Modifi cation of Diet in Renal Disease (MDRD) and CKDEPI, or cystatin C to improve glomerular fi ltration rate estimation; 3) to take into account the oxidative stress testifying of a bad recovery; and 4) better to take care the nutritional status of the players by adapting needs and amino acids supplementations but also to consider a follow-up of oxidative stress and antioxidants according our results.

PURPOSE. To assess the associations of plasma lutein and zeaxanthin and other carotenoids with the risk of age-related maculopathy (ARM) and cataract in the population-based Pathologies Oculaires Liees a l'Age (POLA) Study. METHODS. Retinal photographs were graded according to the international classification. ARM was defined by the presence of late ARM (neovascular ARM, geographic atrophy) and/or soft indistinct drusen (>125 μm) and/or soft distinct drusen (>125 μm) associated with pigmentary abnormalities. Cataract classification was based on a direct standardized lens examination at the slit lamp, according to Lens Opacities Classification System III. Plasma carotenoids were measured by high-performance liquid chromatography (HPLC), in 899 subjects of the cohort. RESULTS. After multivariate adjustment, the highest quintile of plasma zeaxanthin was significantly associated with reduced risk of ARM (OR = 0.07; 95% CI: 0.01-0.58; P for trend = 0.005), nuclear cataract (OR = 0.23; 95% CI: 0.08-0.68; P for trend = 0.003) and any cataract (OR = 0.53; 95% CI: 0.31-0.89; P for trend = 0.01). ARM was significantly associated with combined plasma lutein and zeaxanthin (OR = 0.21; 95% CI: 0.05- 0.79; P for trend = 0.01), and tended to be associated with plasma lutein (OR = 0.31; 95% CI: 0.09-1.07; P for trend = 0.04), whereas cataract showed no such associations. Among other carotenoids, only β-carotene showed a significant negative association with nuclear cataract, but not ARM. CONCLUSIONS. These results are strongly suggestive of a protective role of the xanthophylls, in particular zeaxanthin, for the protection against ARM and cataract.