Performance and Suitability of Mindray BS480©: A Fully Open Clinical Chemistry Analyzer.

BACKGROUND: Mindray BS480©, a multi-parametric and random-access clinical chemistry instrument, is suitable for medium-sized hospital applications. Large laboratories in hospital environments require high throughput non-emergency settings that could slow routine production lines. In addition, the possibility to adapt to different methodologies is of great convenience for improving the transfer from manual to automated applications. The aim of the study is to evaluate analytical performances and to draw a comparison between analyzers for most common clinical parameters under simulated routine conditions. METHOD: Analytical performances in term of imprecision and comparison studies were performed between Mindray BS480© and reference analyzers such as Cobas 8000© for 12 routine parameters and ABX Pentra 400© for pyruvate and acetoacetate. Mindray BS480© usability, in terms of throughput and emergency sample handling, was also evaluated. RESULTS: Imprecision CVs for different analytes ranged from 0.7% to 7.9%, and the comparison study regression slope ranged from 0.74 to 1.22. Mindray workflow and emergency modes covered automated specifications. CONCLUSION: Results are considered significant for colorimetric, turbidimetric and ISE assays. Most performances were in line with Mindray and current recommendations. Mindray BS480© provides precise measurements for a variety of analytes. The possibility to adapt some methodologies is very useful, leading to a switch from manual methodology to automation.

Characterization and identification of eight designer benzodiazepine metabolites by incubation with human liver microsomes and analysis by a triple quadrupole mass spectrometer.

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.

Vitamin E-coated polysulfone membrane improved red blood cell antioxidant status in hemodialysis patients.

BACKGROUND: Oxidative stress has emerged as a strong pathogenic cofactor implicated in the development of long-term complications in hemodialysis (HD) patients, such as anemia, and as a major component of the malnutrition inflammation complex syndrome. This prospective multicenter study aimed at evaluating the short-term effects of the new vitamin E (vitE)-coated polysulfone (PS) membrane (VitabranE) on biocompatibility performances and anemia in HD patients. METHODS: After a 3-month washout period with a high-flux synthetic dialyzer, 43 HD patients were switched to a vitE-PS dialyzer. Sampling was performed at baseline (corresponding to the end of the washout period) and after 1, 2 and 3 months of treatment. Oxidative stress status, as well as inflammatory parameters, was investigated at the end of each study period. Hemoglobin levels and administered doses of recombinant human erythropoietin or epoetin (EPO) were available in each center. RESULTS: The use of vitE-coated membranes for 3 months was not associated with any change in inflammatory parameters. By contrast, vitE-PS dialyzer resulted in a progressive increase in red blood cell (RBC) vitE concentration and in RBC superoxide dismutase activity. A concomitant progressive significant decrease in advanced oxidation protein product concentration at 2 months was observed, suggesting a preventive effect on oxidative stress. Finally, a significant decrease of the erythropoietin resistance index was obtained after 3 months of treatment. CONCLUSIONS: Use of the vitE-PS membrane during a short period improves erythrocyte antioxidant defense mechanisms and seems to lead to a reduction in EPO requirements in HD patients.

Antioxidant and oligonutrient status, distribution of amino acids, muscle damage, inflammation, and evaluation of renal function in elite rugby players.

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. Specific 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 specifically determined for our study during a pre-competition period (September 2008 and 2009). RESULTS: Globally, no deficit 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 specific 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-specific reference intervals for CK and creatinine parameters; 2) the use of enzymatic creatinine for Modification of Diet in Renal Disease (MDRD) and CKD-EPI, or cystatin C to improve glomerular filtration 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.

Carbon monoxide exposure enhances arrhythmia after cardiac stress: involvement of oxidative stress.

Arrhythmias following cardiac stress are a key predictor of death in healthy population. Carbon monoxide (CO) is a ubiquitous pollutant promoting oxidative stress and associated with hospitalization for cardiovascular disease and cardiac mortality. We investigated the effect of chronic CO exposure on the occurrence of arrhythmic events after a cardiac stress test and the possible involvement of related oxidative stress. Wistar rats exposed chronically (4 weeks) to sustained urban CO pollution presented more arrhythmic events than controls during recovery after cardiac challenge with isoprenaline in vivo. Sudden death occurred in 22% of CO-exposed rats versus 0% for controls. Malondialdehyde (MDA), an end-product of lipid peroxidation, was increased in left ventricular tissue of CO-exposed rats. Cardiomyocytes isolated from CO-exposed rats showed higher reactive oxygen species (ROS) production (measured with MitoSox Red dye), higher diastolic Ca(2+) resulting from SR calcium leak and an higher occurrence of irregular Ca(2+) transients (measured with Indo-1) in comparison to control cells after a high pacing sequence. Acute treatment with a ROS scavenger (N-acetylcysteine, 20 mmol/L, 1 h) prevented this sequence of alterations and decreased the number of arrhythmic cells following high pacing. Chronic CO exposure promotes oxidative stress that alters Ca(2+) homeostasis (through RYR2 and SERCA defects) and thereby mediates the triggering of ventricular arrhythmia after cardiac stress that can lead to sudden death.

Phycobiliprotein C-phycocyanin from Spirulina platensis is powerfully responsible for reducing oxidative stress and NADPH oxidase expression induced by an atherogenic diet in hamsters.

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.

Plasma lutein and zeaxanthin and other carotenoids as modifiable risk factors for age-related maculopathy and cataract: the POLA Study.

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 Liées à 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 microm) and/or soft distinct drusen (>125 microm) 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 beta-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.

Associations of cataract with antioxidant enzymes and other risk factors: the French Age-Related Eye Diseases (POLA) Prospective Study.

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 Liées à l'Age, POLA) Study included 2584 residents of Sète (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) > or = 4 for nuclear cataract, C > or = 4 for cortical cataract, and P > or = 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.