Le système NAD(P)H oxydase vasculaire (une cible préventive de l'athérosclérose)

La NAD(P)H oxydase vasculaire est un element clé dans le développement de maladies cardiovasculaires, comme l'hypertension, le diabète et l'athérosclérose, et la production d'anion superoxyde par les cellules vasculaires contribuent au stress oxydant. Dans une première partie, nous avons observé une diminution de la formation des stries lipidiques, l'émergence de l'athérosclérose, la production d'anion superoxyde et l'expression de la NAD(P)H oxydase cardiaque avec la supplémentation en extrait de fruits et légumes ou en spiruline et phycocyanine préparées à partir de spiruline faible ou riche en sélénium. Dans une seconde partie, nous avons observé l'effet préventif de molécules polyphénoliques sur les altérations cardiaques, comme la fibrose et l'hypertrophie, associé au syndrome métabolique chez des rats high fructose. Dans une troisième partie, nous avons examiné l'effet préventif des polyphénols sur le développement de l'obésité. D'une part, la consommation chronique de tannins de pépins de raisins a des effets bénéfiques sur le développement du stress oxydant, potentiellement impliqué dans les complications cardiovasculaires chez le hamster syrien doré. D'autre part, nous avons étudié les systèmes mitochondriaux et NAD(P)H oxydase et le stress oxydant dans le foie, le cœur et le muscle squelettique de rats high-fat high-sucrose. Un extrait de polyphénols du vin prévient partiellement le développement du stress oxydant. Finalement, nous avons démontré que le b-glycérophosphate ou le sérum urémique induisent l'augmentation de la production d'H2O2 et l'expression de la NAD(P)H oxydase. Le stress oxydant induit par le b-glycérophosphate est associé avec une expression précoce du Core binding factor a1 et de l'alcaline phosphatase suggérant un implication majeure de NAD(P)H oxydase vasculaire dans l'augmentation des calcifications vasculairesVascular NAD(P)H oxidase is a well-recognized feature in the development of cardiovascular diseases such as hypertension, diabetes and atherosclerosis, and superoxide-anion production by vascular cells may contribute significantly to oxidative stress. In the first part, we have observed a decrease of fatty streak formation, atherosclerosis emergence, cardiac superoxide production and NAD(P)H oxidase expression with the supplementation of fruits and vegetables extract or spirulina and phycocyanin, prepared from low-selenium or Se-rich spirulina. In the second part, we have observed the preventive effect of polyphenolic molecules on cardiac alterations, such as fibrosis and hypertrophy, associated with metabolic syndrome in rats fed a high fructose. In the third part, we have examined the preventive effect of polyphenols on the development of obesity. On the one hand, chronic consumption of grape seed tannins has potential beneficial effects with respect to the development of oxidative stress potentially involved in cardiovascular complications in golden Syrian hamster. On the other hand, we have investigated mitochondrial and NADPH oxydase systems and oxidative stress in liver, heart and skeletal muscle of rats fed a high-fat high-sucrose. Wine polyphenol extract was shown to partially prevent from oxidative stress development. Finally, we have demonstrated that b-glycerophosphate or uremic serum increased H2O2 and NAD(P)H oxidase expression. b-glycerophosphate-induced oxidative stress was associated with an early expression Core binding factor a1 and ALP expression suggesting a major implication of vascular NAD(P)H oxidase in the increase of vascular calcificationMONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Enrichment of pasta with faba bean does not impact glycemic or insulin response but can enhance satiety feeling and digestive comfort when dried at very high temperature

Enrichment of durum wheat pasta with legume flour enhances their protein and essential amino acid content, especially lysine content. However, despite its nutritional potential, the addition of a legume alters the rheological properties of pasta. High temperature drying of pasta reduces this negative effect by strengthening its protein network. The aim of our study was to determine if these changes in pasta structure alter its in vitro carbohydrate digestibility, in vivo glycemic, insulin and satiety responses. We also investigated if high temperature drying of pasta can reduce the well-known digestive discomfort associated with the consumption of legume grains. Fifteen healthy volunteers consumed three test meals: durum wheat pasta dried at a low temperature (control), and pasta enriched with 35% faba bean dried at a low and at a very high temperature. When enriched with 35% legume flour, pasta kept its nutritionally valuable low glycemic and insulin index, despite its weaker protein network. Drying 35% faba bean pasta at a high temperature strengthened its protein network, decreased its in vitro carbohydrate digestion with no further decrease in its in vivo glycemic or insulin index. Drying pasta at a very high temperature reduced digestive discomfort and enhanced self-reported satiety, and was not associated with a modification of energy intake in the following meal

Evaluation of QMS Everolimus Assay Using Indiko Analyzer

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Factors of microinflammation in non-diabetic chronic kidney disease: a pilot study

International audienceThe relationships between digestive bacterial translocation, uremic toxins, oxidative stress and microinflammation in a population of chronic kidney disease (CKD) patients without metabolic nor inflammatory disease are unknown.Background The relationships between digestive bacterial translocation, uremic toxins, oxidative stress and microinflammation in a population of chronic kidney disease (CKD) patients without metabolic nor inflammatory disease are unknown. Methods Bacterial translocation, uremic toxins, oxidative stress, and inflammation were assessed by measuring plasma levels of 16S ribosomal DNA (16S rDNA), p-cresyl sulfate (PCS), indoxyl sulfate (IS), indole acetic acid (IAA), F2-isoprostanes, hsCRP and receptor I of TNF alpha (RITNF alpha) in patients without metabolic nor inflammatory disease. 44 patients with CKD from stage IIIB to V and 14 controls with normal kidney function were included from the nephrology outpatients. 11 patients under hemodialysis (HD) were also included. Correlations between each factor and microinflammation markers were studied. Results 16S rDNA levels were not increased in CKD patients compared to controls but were decreased in HD compared to non-HD stage V patients (4.7 (3.9-5.3) vs 8.6 (5.9-9.7) copies/mu l, p = 0.002). IS, PCS and IAA levels increased in HD compared to controls (106.3 (73.3-130.4) vs 3.17 (2.4-5.1) mu mol/l, p = 5 mg/l (p = 0.01, 0.04 and 0.001 respectively). 16S rDNA, F2-isoprostanes were not correlated to microinflammation markers in our study. Conclusions In CKD patients without any associated metabolic nor inflammatory disease, only PCS, IS, and urea were correlated with microinflammation. Bacterial translocation was decreased in patients under HD and was not correlated to microinflammation

Intergenerational effects on mouse sperm quality after in utero exposure to acetaminophen and ibuprofen

International audienceNonsteroidal antiinflammatory drugs and analgesic drugs, such as N-acetyl- p-aminophenol (APAP; acetaminophen, paracetamol), are widely used by pregnant women. Accumulating evidence has indicated that these molecules can favor genital malformations in newborn boys and reproductive disorders in adults. However, the consequences on postnatal testis development and adult reproductive health after exposure during early embryogenesis are still unknown. Using the mouse model, we show that in utero exposure to therapeutic doses of the widely used APAP-ibuprofen combination during the sex determination period leads to early differentiation and decreased proliferation of male embryonic germ cells, and early 5-methylcytosine and extracellular matrix protein deposition in 13.5 d postcoitum exposed testes. Consequently, in postnatal testes, Sertoli-cell maturation is delayed, the Leydig-cell compartment is hyperplasic, and the spermatogonia A pool is decreased. This results in a reduced production of testosterone and in epididymal sperm parameter defects. We observed a reduced sperm count (19%) in utero-exposed (F0) adult males and also a reduced sperm motility (40%) in their offspring (F1) when both parents were exposed, which leads to subfertility among the 6 mo old F1 animals. Our study suggests that the use of these drugs during the critical period of sex determination affects the germ-line development and leads to adverse effects that could be passed to the offspring.-Rossitto, M., Marchive, C., Pruvost, A., Sellem, E., Ghettas, A., Badiou, S., Sutra, T., Poulat, F., Philibert, P., Boizet-Bonhoure, B. Intergenerational effects on mouse sperm quality after in utero exposure to acetaminophen and ibuprofen

Xanthine oxidase is variably involved in nutritional and physio-pathologic oxidative stress situations

Background: High random ROS production leads to generalised oxidative stress that is involved in aging and degenerative diseases, such diabetes or chronic kidney failure. The major cellular ROS sources are mitochondria and NADPH oxidase, and xanthine oxidase (XO). XO is known to be involved in ischemiareperfusion oxidative stress damages, but little is known about its possible involvement in other nutritional and physio-pathologic oxidative stress situations. Objective: The objective of this study is to determine the effect on xanthine oxidase activity in nutritional and pathological oxidative stress conditions. Methods: In this research, we investigated the contribution of XO activity in the oxidative stress situations as metabolic syndrome or chronic kidney failure. For this aim, we have determined tissue XO activity in rats subjected to different nutritional and pathological oxidative stress conditions. Results: Our results show that XO does not seem to be major contributor to the oxidative stress observed in the rats fed with high fat, or high fat/high sucrose/fructose diets. However, XO activity increased in chronic kidney failure, caused by adenine administration or by nephrectomy. Moreover, significant correlations have been observed between XO activity and some oxidative stress parameters. Conclusion: These results clarify the possible involvement of XO activity in physio-pathological oxidative stress conditions. More studies are needed in the future to determine the XO activity in other physio-pathological oxidative stress models, in order to elaborate a comprehensible view on the involvement of the XO activity in these physio-pathological oxidative stress conditions

Biomarkers of Redox Balance Adjusted to Exercise Intensity as a Useful Tool to Identify Patients at Risk of Muscle Disease through Exercise Test

International audienceThe screening of skeletal muscle diseases constitutes an unresolved challenge. Currently, exercise tests or plasmatic tests alone have shown limited performance in the screening of subjects with an increased risk of muscle oxidative metabolism impairment. Intensity-adjusted energy substrate levels of lactate (La), pyruvate (Pyr), β-hydroxybutyrate (BOH) and acetoacetate (AA) during a cardiopulmonary exercise test (CPET) could constitute alternative valid biomarkers to select “at-risk” patients, requiring the gold-standard diagnosis procedure through muscle biopsy. Thus, we aimed to test: (1) the validity of the V’O2-adjusted La, Pyr, BOH and AA during a CPET for the assessment of the muscle oxidative metabolism (exercise and mitochondrial respiration parameters); and (2) the discriminative value of the V’O2-adjusted energy and redox markers, as well as five other V’O2-adjusted TCA cycle-related metabolites, between healthy subjects, subjects with muscle complaints and muscle disease patients. Two hundred and thirty subjects with muscle complaints without diagnosis, nine patients with a diagnosed muscle disease and ten healthy subjects performed a CPET with blood assessments at rest, at the estimated 1st ventilatory threshold and at the maximal intensity. Twelve subjects with muscle complaints presenting a severe alteration of their profile underwent a muscle biopsy. The V’O2-adjusted plasma levels of La, Pyr, BOH and AA, and their respective ratios showed significant correlations with functional and muscle fiber mitochondrial respiration parameters. Differences in exercise V’O2-adjusted La/Pyr, BOH, AA and BOH/AA were observed between healthy subjects, subjects with muscle complaints without diagnosis and muscle disease patients. The energy substrate and redox blood profile of complaining subjects with severe exercise intolerance matched the blood profile of muscle disease patients. Adding five tricarboxylic acid cycle intermediates did not improve the discriminative value of the intensity-adjusted energy and redox markers. The V’O2-adjusted La, Pyr, BOH, AA and their respective ratios constitute valid muscle biomarkers that reveal similar blunted adaptations in muscle disease patients and in subjects with muscle complaints and severe exercise intolerance. A targeted metabolomic approach to improve the screening of “at-risk” patients is discussed

Evaluation of a new point-of-care testing for creatinine and urea measurement

International audiencePoint of care testing makes it possible to obtain results in an extremely short time. Recently, radiometer has expanded the panel of tests available on its ABL90 FLEX PLUS blood gas analyzer (ABL90) by adding urea and creatinine. The aim of this study was to verify the performance of these new parameters. This included assessment of imprecision, linearity, accuracy by comparison with central laboratory standard assays and interferences. In addition, clinical utility in a dialysis center was evaluated. Within-lab coefficients of variation were close to 2%. The mean and limits of agreement (mean ± 1.96 SD) of the difference between ABL90 and Roche enzymatic assays on cobas 8000 were 0.5 (from -1.4 to 2.3) mmol/L and -0.9 (from -19.5 to 17.8) µmol/L for urea and creatinine, respectively. The ABL90 enzymatic urea and creatinine assays met the acceptance criteria based on biological variation for imprecision and showed good agreement with central laboratory. The two assays were unaffected by hematocrit variation between 20 and 70%, hemolysis and icterus interferences. It should be noted that the relationship between lab methods and ABL90 was conserved even for high pre-dialysis values allowing easy access to dialysis adequacy parameters (Kt/V) and muscle mass evaluation (creatinine index). Rapid measurement of creatinine and urea using whole blood specimens on ABL90 appears as a fast and convenient method. Analytical performances were in accordance with our expectations without any significant interferences by hemolysis or icterus