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International audience; Background: Inflammation is involved during acute myocardial infarction, and could be an interesting target to prevent ischaemia-reperfusion injuries. Colchicine, known for its pleiotropic anti-inflammatory effects, could decrease systemic inflammation in this context.Aims: To evaluate the impact of colchicine on inflammation in patients admitted for ST-segment elevation myocardial infarction (STEMI).Methods: All patients admitted for STEMI with one of the main coronary arteries occluded, and successfully treated with percutaneous coronary intervention, were included consecutively. Patients were randomized to receive either 1 mg colchicine once daily for 1 month plus optimal medical treatment or optimal medical treatment only. C-reactive protein (CRP) was assessed at admission and daily until hospital discharge. The primary endpoint was CRP peak value during the index hospitalization.Results: Forty-four patients were included: 23 were treated with colchicine; 21 received conventional treatment only. At baseline, both groups were well balanced regarding age, sex, risk factors, thrombolysis in myocardial infarction flow and reperfusion delay. The culprit artery was more often the left anterior descending artery in the colchicine group (P = 0.07), reflecting a more severe group. There was no significant difference in mean CRP peak value between the colchicine and control groups (29.03 mg/L vs 21.86 mg/L, respectively; P = 0.36), even after adjustment for type of culprit artery (26.99 vs 24.99 mg/L, respectively; P = 0.79).Conclusion: In our study, the effect of colchicine on inflammation in the context of STEMI could not be demonstrated. Further larger studies may clarify the impact of colchicine in acute myocardial infarction.; Contexte: L’inflammation, impliquée au cours de l’infarctus du myocarde, pourrait représenter une cible thérapeutique intéressante et limiter les lésions d’ischémie-reperfusion. La colchicine, aux effets anti-inflammatoires pléiotropes, pourrait diminuer l’inflammation systémique au cours de l’infarctus du myocarde.Objectif: Évaluer l’impact de la colchicine sur l’inflammation systémique, dans l’infarctus du myocarde avec sus-décalage du segment ST.Méthodes: Tous les patients admis pour infarctus du myocarde avec occlusion de l’une des trois artères principales traités avec succès par angioplastie primaire étaient inclus de manière consécutive. Ils étaient randomisés pour recevoir 1 mg de colchicine par jour pendant 1 mois, en sus du traitement médical optimal, ou le traitement médical optimal seul. La C-réactive protéine était dosée à l’admission et quotidiennement jusqu’à la sortie. Le critère de jugement principal était le pic de CRP au cours de l’hospitalisation.Résultats: Quarante-quatre patients ont été inclus, 23 ont reçu la colchicine et 21 le traitement conventionnel seul. Les caractéristiques de base étaient comparables entre les 2 groupes concernant l’âge, le sexe, les facteurs de risque cardiovasculaires, le flux TIMI et le délai de reperfusion. L’artère interventriculaire antérieure était le plus souvent l’artère coupable dans le groupe colchicine (p = 0,07) reflétant un groupe plus sévère. Il n’y avait aucune différence significative entre les 2 groupes concernant la valeur du pic de CRP (29,03 mg/L dans le groupe colchicine vs 21,86 mg/L dans le groupe témoin ; p = 0,36), même après ajustement sur le type d’artère coupable (26,99 vs 24,99 mg/L ; p = 0,79).Conclusion: Aucun effet de la colchicine sur l’inflammation systémique dans l’infarctus du myocarde n’a pu être démontré. Des études complémentaires de plus grande envergure apparaissent nécessaires pour clarifier l’impact de la colchicine dans l’infarctus du myocarde.

Objectif Explorer les liens entre les taux d’orexine(ORX) dans le liquide cephalo-rachidien et des marqueurs de fragmentation du sommeil nocturne a la polysomnographie(PSG). Methodes Les PSG de 300 sujets non traites (45 % F, 30 ± 16 ans, ORX 155 ± 154 pg/mL) ont ete analysees. Les marqueurs etudies etaient : les Wake Bouts (WB) (sequence continue d’epoques de veille apres endormissement), Sleep Bouts (SB) (sequence continue d’epoques de sommeil), et transitions veille/sommeil. Les sujets ont ete categorises en fonction de l’ORX : en tertiles (≤ 26, [26 ;254], > 254 pg/mL) et en 2 categories (110 pg/mL) ; et compares par des modeles de regression logistiques ; les resultats ajustes sur âge, sexe et IMC. Resultats Les sujets dans le tertile d’ORX bas avaient plus de transitions, et un nombre de WB plus eleve que ceux dans les tertiles moyen et haut, avec un effet dose (45,33,25, p 2 min) qui augmentaient (9.6,10.4,13.4 %, p = 0.0001). Le nombre de SB augmentait quand l’ORX diminuait (26,34,45, p Conclusion Cette etude objective l’effet direct de l’ORX sur la stabilisation du sommeil. Les SB et WB sont des biomarqueurs de la fragmentation du sommeil, fortement correles aux taux d’ORX, avec un effet dose-dependant.

Objectives We report the analytical performances of the Lumipulse®G BRAHMS PCT assay (Fujirebio, Courteboeuf, France) and the concordance with BRAHMS PCT Kryptor CompactPlus© results from central laboratory. Design and methods Lumipulse®G BRAHMS PCT immunoassay on Lumipulse®G600II instrument is a chemiluminescence enzyme immunoassay (CLEIA). Analytical performances included imprecision study, linearity, limit of detection and comparison study on 138 plasma specimen on Lumipulse®G600II vs plasma on Kryptor CompactPlus©. Results The intra and inter assay imprecision of Lumipulse®G BRAHMS PCT was between 2 and 5%. The LoD in our condition was 0.0029 ng/mL in accordance with the LoD provided by the manufacturer (0.0048 ng/mL). The linear equation of linearity was y = 1,001 × − 0,052 with r 2 = 0.99, with a mean recovery (SD) percentage of 1.8% (8%). Correlation studies showed a good correlation (r = 0.99) between plasma on Kryptor and Lumipulse, with a bias of 0.02 in the range from 0.12 to 1 ng/mL. Conclusion The new adaptation developed from Fujirebio on quantification of PCT with CLEIA technology from monoclonal antibodies from ThermoFisher appears to be acceptable for clinical use.

Introduction Polycystic kidney disease is associated with an increased cardiovascular risk in humans. Hypertrophy and impaired relaxation of the heart can be early signs of cardiac dysfunction even with preserved ejection fraction (EF). Objective The aim of the study was to evaluate cardiac alterations in rats with polycystic kidney (PCK). Particularly, the chronological sequence of renal and cardiac damages was assessed. Methods PCK and control rats were studied at 3, 6, and 9 months of age. Renal function was determined with the level of plasma creatinine and urea. Arterial pressure, cardiac hypertrophy (weight), cardiac fibrosis (Sirius red staining), cardiac functional parameters E/A and E/E’ were performed by cardiac echography. Cardiac expression of cardiokines were analyzed by RT-qPCR to investigate the secretory heart function and the signalization implicated in the cardiac alteration. Results At 9 mo., PCK rats exhibited elevated plasma creatinine and urea, increased arterial pressure, and higher heart weight index. Cardiac fibrosis was higher in PCK rats, increased with time, and was doubled compared to controls at the age of 9 months. Both E/A and E/E’ were reduced in 9 mo. PCK rats while ejection fraction was preserved. Expression of Apelin was reduced and GDF15 was increased at this time. At 6 months of age, kidney function and ejection fraction were maintained. Yet, E/A and E/E’ were already altered despite no significant elevation of cardiac mass and fibrosis. In addition, cardiokines profile was also modified at 6 mo. At the age of 3 months, none of the parameters studied was different in PCK compared to control rats. Conclusion Diastolic function was modified before the clear reduction of renal function and cardiac ejection fraction. On the other hand, when renal function began to degrade there was an acceleration of alterations of cardiac function and cardiokines profile coupled with development of moderate arterial hypertension.

Introduction Heart failure is a leading cause of hospitalization, morbidity and mortality. Treatments are not up-titrated for all patients because of adverse effects. Strategies to better discriminate patients who may benefit most from titration are needed to improve the benefit-risk balance. Soluble suppression of tumorigenicity-2 (sST2) is a new prognostic biomarker of heart failure. Patients with a high baseline sST2 levels could benefit the most from cardioprotective treatments. Purpose The current study considered sST2 value as a guide for medical management in patients admitted for acute HF decompensation, in an attempt to minimize hospital readmission. Methods STADE-HF (sST2 As a help for management of Diagnosis, Evaluation and management of HF) was a blinded prospective randomized controlled trial and included 123 patients admitted for heart failure between January 2017 and August 2018 for acute HF. There were randomized into 2 groups: Usual treatment group, in which patient's sST2 level was unknown, and interventional treatment group, for whom sST2 level was known and used on day 4 of hospitalization for guide the treatment. The main clinical endpoint was the readmission rate for any cause at 1 month. Results The primary endpoint of readmission during the first month follow-up was observed in 28 patients (25%); 10 patients (19%) in the usual group, and 18 (32%) in the sST2 group without statistical difference (P = 0.11). The mean duration of hospitalization was lower in patients with low sST2 ( 37 ng/mL, P = 0.003). Conclusion The STADE-HF study failed to decrease readmissions for patients admitted for acute HF. A long-term follow-up is conducted to evaluate the effect on cardiovascular hospitalization and mortality at one year after index hospitalization.

Introduction La sclerodermie systemique (ScS) est une maladie incurable dans laquelle des strategies innovantes sont toujours recherchees pour lutter contre la fibrose tissulaire. Parmi les nouvelles approches anti-fibrotiques, la therapie cellulaire basee sur l’utilisation de cellules souches (stromales) mesenchymateuses (CSM) semble prometteuse. Nous avons precedemment rapporte les effets anti-fibrotiques des CSM dans un modele experimental de ScS induit par l’acide hypochloreux (ScS-HOCl) [1] , [2] , [3] . Nous avons montre que ces effets etaient sous-tendus par plusieurs mecanismes d’action, dont une action immunosuppressive, mais aussi l’activation du remodelage tissulaire et des defenses anti-oxydantes. L’immunomodulation etant un mecanisme majeur dans l’action therapeutique des CSM, nous avons decide d’etudier le role specifique des principales molecules connues comme associees aux proprietes immunosuppressives des CSM. Nous avons ainsi emis l’hypothese que des CSM deficientes pour ces molecules seraient moins efficaces pour reduire la fibrose dans la ScS. Materiels et methodes La ScS-HOCl a ete induite par des injections intradermiques quotidiennes d’HOCl durant 6 semaines chez la souris. Les CSM ont ete isolees de la moelle osseuse de souris sauvages (WT) ou de souris knock-out pour IL1RA, IL6 ou iNOS (respectivement CSM-IL1RA-/-, -IL6-/-ou -iNOS-/-). Les souris traitees ont recu une perfusion intraveineuse de 2,5 × 10e5 CSM a J21. L’epaisseur de la peau, ainsi que les parametres histologiques et biologiques, ont ete evalues dans le serum et la peau a J42. Resultats Les CSM-IL1RA-/- et - IL6-/- exercaient des proprietes anti-fibrotiques similaires a celles du CSM-WT, avec une reduction de l’epaisseur de la peau et des depots de collagenes tissulaires. Inversement, les CSM-iNOS-/- n’exercaient pas de fonction anti-fibrotique comme le montre une progression d’epaisseur de peau similaire a celle des souris ScS-HOCl non traitees. Comparees aux CSM-WT, les CSM-iNOS-/- conservaient certaines proprietes immunosuppressives et de remodelage tissulaire, mais perdaient leurs capacites a reduire le stress oxydant chez les souris ScS-HOCl. Conclusion Notre etude met en evidence le role crucial de iNOS, dont l’activite est requise pour leurs proprietes therapeutiques anti-fibrotiques des CSM, dans le modele experimental de ScS-HOCl. Les fonctions anti-oxydantes liees au NO semblent avoir un role determinant dans la lutte contre la fibrose tissulaire dans ce modele pre-clinique de ScS diffuse.

A new method was developed by Roche for the measurement of plasma calcium using the chromophore 5-nitro-5'-methyl-(1,2-bis(o-aminophenoxy)ethan-N,N,N',N'-tetraacetic acid (NM-BAPTA) which could have several advantages over the CPC method. The aim of our study was to evaluate the analytical performances of the NM-BAPTA assay from Roche on c701/Cobas 8000® and to perform a comparison study of calcium values with CPC and Arsenazo III methods.The analytical performance including imprecision study, linearity, and stability of the NM-BAPTA assay was tested on the c701/Cobas 8000®analyzer. The most frequent interferences such as magnesium and gadolinium-based contrast agents (Gd-CAs) were examined with spiked human plasma on the selected method. The calcium Arsenazo III method from Horiba (Montpellier, France) installed on ABX Pentra 400® was used as a reference method. Linear regression analysis was performed to compare data from the different methods.The CV of the NM-BAPTA assay showed good analytical performances with CV1.5%, in agreement with the proposed and interim European biologic goals. We found no interference neither with gadobenate dimeglumine nor with gadoteric acid considering significant findings as interference greater than 5%. In the analytical range from 0.85 to 3.80 mmol/L, the NM-BAPTA method was closely correlated to the Arsenazo III method.Our data demonstrate that this new calcium NM-BAPTA method developed by Roche analyzers perform as well as the conventional method, especially for the outermost values. Thus, this new colorimetric assay could substitute the CPC method on Roche analyzers.

Recent advances in the identification of susceptibility genes and environmental exposures provide strong support that narcolepsy-cataplexy is an immune-mediated disease. Only few serum cytokine studies with controversial results were performed in narcolepsy and none in the cerebrospinal fluid. We measured a panel of 12 cytokines by a proteomic approach in the serum of 35 patients with narcolepsy-cataplexy compared to 156 healthy controls, and in the cerebrospinal fluid of 34 patients with narcolepsy-cataplexy compared to 17 non-narcoleptic patients; and analyzed the effect of age, duration and severity of disease on the cytokine levels. After multiple adjustments we reported lower serum IL-2, IL-8, TNF-α, MCP-1 and EGF levels, and a tendency for higher IL-4 level in narcolepsy compared to controls. Significant differences were only found for IL-4 in cerebrospinal fluid, being higher in narcolepsy. Positive correlations were found in serum between IL-4, daytime sleepiness, and cataplexy frequency. The expression of some pro-inflammatory cytokines (MCP-1, VEGF, EGF, IL2, IL-1β, IFN-γ) in either serum or CSF was negatively correlated with disease severity and duration. No correlation was found for any specific cytokine in 18 of the patients with narcolepsy with peripheral and central samples collected the same day. Significant decreased pro/anti-inflammatory cytokine profiles were found at peripheral and central levels in narcolepsy, together with a T helper 2/Th1 serum cytokine secretion imbalance. To conclude, we showed some evidence for alterations in the cytokine profile in patients with narcolepsy-cataplexy compared to controls at peripheral and central levels, with the potential role of IL-4 and significant Th1/2 imbalance in the pathophysiology of narcolepsy.

The National Kidney Disease Education Program group demonstrated that MDRD equation is sensitive to creatinine measurement error, particularly at higher glomerular filtration rates. Thus, MDRD-based eGFR above 60 mL/min/1.73 m2 should not be reported numerically. However, little is known about the impact of analytical error on CKD-EPI-based estimates. This study aimed at assessing the impact of analytical characteristics (bias and imprecision) of 12 enzymatic and 4 compensated Jaffe previously characterized creatinine assays on MDRD and CKD-EPI eGFR. In a simulation study, the impact of analytical error was assessed on a hospital population of 24 084 patients. Ability using each assay to correctly classify patients according to chronic kidney disease (CKD) stages was evaluated. For eGFR between 60 and 90 mL/min/1.73 m2, both equations were sensitive to analytical error. Compensated Jaffe assays displayed high bias in this range and led to poorer sensitivity/specificity for classification according to CKD stages than enzymatic assays. As compared to MDRD equation, CKD-EPI equation decreases impact of analytical error in creatinine measurement above 90 mL/min/1.73 m2. Compensated Jaffe creatinine assays lead to important errors in eGFR and should be avoided. Accurate enzymatic assays allow estimation of eGFR until 90 mL/min/1.73 m2 with MDRD and 120 mL/min/1.73 m2 with CKD-EPI equation.

Oxidative stress is involved in obesity. However, dietary antioxidants could prevent oxidative stress-induced damage. We have previously shown the preventive effects of a melon superoxide dismutase.(SODB) on oxidative stress. However, the mechanism of action of SODB is still unknown. Here, we evaluated the effects of a 1-month curative supplementation with SODB on the liver of obese hamsters. Golden Syrian hamsters received either a standard diet or a cafeteria diet composed of high-fat, high-sugar, and high-salt supermarket products, for 15 weeks. This diet resulted in insulin resistance and in increased oxidative stress in the liver. However, inflammatory markers (IL-6, TNF-alpha, and NF-kappa B) were not enhanced and no liver steatosis was detected, although these are usually described in obesity-induced insulin resistance models. After the 1-month supplementation with SODB, body weight and insulin resistance induced by the cafeteria diet were reduced and hepatic oxidative stress was corrected. This could be due to the increased expression of the liver antioxidant defense proteins (manganese and copper/zinc superoxide dismutase, catalase, and glutathione peroxidase). Even though no inflammation was detected in the obese hamsters, inflammatory Markers were decreased after SODB supplementation, probably through the reduction of oxidative stress. These findings suggest for the first time that SODB could exert its antioxidant properties by inducing the endogenous antioxidant defense. The mechanisms underlying this induction need to be further investigated. (C) 2013 Elsevier Inc. All rights reserved.

We sought to evaluate the added value of ultrasensitive copeptin (us-copeptin) for early rule out of acute myocardial infarction in a prospective cohort of emergency department (ED) patients with acute chest pain.This was a prospective study including consecutive patients with acute chest pain presenting to the ED within 12 hours of symptom onset. High-sensitivity cardiac troponin T (hs-cTnT, Roche Diagnostics, Meylan, France) and us-copeptin (ThermoFisher Scientific, Clichy, France) were blindly assayed from venous blood samples obtained at admission. Diagnosis was made by 2 ED physicians using all available data and serial cardiac troponin I as the biochemical standard. Diagnostic performances of us-copeptin combined with hs-cTnT were assessed using logistic regression. Analysis was conducted in all patients and in patients without ST-elevation myocardial infarction.A total of 194 patients were included (age, 61 [48-75] years; male sex, 63%). Acute myocardial infarction occurred in 52 (27%) patients, including non-ST-elevation myocardial infarction (NSTEMI) in 25 (13%). Patients with acute myocardial infarction had higher levels of hs-cTnT (50 [95% confidence interval, 19-173] ng/L) and us-copeptin (30 [13-113] pmol/L) at admission compared with those without (P.05). Combination of markers significantly improved receiver operating characteristic area under the curve (from 0.89 [0.85-0.92] for hs-cTnT alone to 0.93 [0.89-0.97], P = .018). Sensitivity and negative predictive value were increased, particularly for NSTEMI diagnosis (sensitivity, 76% [54.9-90.6] to 96% [79.6-99.9]; negative predictive value, 95% [90.4-98.3] to 98.9% [94.2 to 100]).Assessment of us-copeptin combined with hs-cTnT on ED admission could allow safe and early rule out of NSTEMI for patients with negative results on both markers and help identify patients who may be suitable for discharge.

The French Society of Clinical Biochemistry conducted this study to compare the accuracy and performances of the best creatinine enzymatic assays and the compensated Jaffe methods from the same manufacturers. Creatinine was measured in 3 serum pools with creatinine levels of 35.9 ± 0.9 μmol/L, 74.4 ± 1.4 μmol/L, and 97.9 ± 1.7 μmol/L (IDMS determination). The performances of the assays (total error that includes the contribution of bias and imprecision) were evaluated using Monte-Carlo simulations and compared against desirable NKDEP criteria. The enzymatic assays always fell within the desirable total Error of 7.6%. By contrast, this requirement was never obtained for the compensated Jaffe methods at the critical level of 74.4 ± 1.4 μmol/L. Only the compensated Jaffe creatinine on Olympus analyzer reached this specification at 35.9 ± 0.9 and 97.9 ± 1.7 μmol/L levels. This study demonstrates that, despite substantial improvement regarding traceability to the IDMS reference method and precision, compensated Jaffe creatinine methods, by contrast to enzymatic ones, do not reach the desirable specifications of NKDEP at normal levels of creatinine.

Purpose and medical hypothesis: Rest is usually recommended in acute pericarditis, as it could help to lower heart rate (HR) and contribute to limit ‘‘mechanical inflammation’’. Whether HR on admission could be correlated and perhaps participate to inflammation has not been reported. Methods: Between March 2007 and February 2010, we conducted a retrospective study on all patients admitted to our center for acute pericarditis. Diagnosis criteria included two of the following ones: typical chest pain, friction rub, pericardial effusion on cardiac echography, or typical electrocardiogram (ECG) findings. Primary endpoint was biology: CRP on admission, on days 1, 2, 3, and especially peak. Results: We included 73 patients. Median age was 38 years (interquartiles 28–51) and median hospitalization duration was 2.0 days (1.5–3.0). Median heart rate was 88.0 beats per minute (bpm) on admission (interquartiles 76.0–100.0) and 72.0 on discharge (65.0–80.0). Heart rate on admission was significantly correlated with CRP peak (p < 0.001), independently of temperature on admission, hospitalization duration and age. Recurrences occurred within 1 month in 32% of patients. Heart rate on hospital discharge was correlated with recurrence, independently of age. Conclusion: In acute pericarditis, heart rate on admission is independently correlated with CRP levels and heart rate on discharge seems to be independently correlated to recurrence. This could suggest a link between heart rate and pericardial inflammation.

Statin use may be limited by muscle side effects. Although incompletely understood to date, their pathophysiology may involve oxidative stress and impairments of mitochondrial function and of muscle Ca(2+) homeostasis. In order to simultaneously assess these mechanisms, 24 male healthy volunteers were randomized to receive either simvastatin for 80 mg daily or placebo for 8 weeks. Blood and urine samples and a stress test were performed at baseline and at follow-up, and mitochondrial respiration and Ca(2+) spark properties were evaluated on a muscle biopsy 4 days before the second stress test. Simvastatin-treated subjects were separated according to their median creatine kinase (CK) increase. Simvastatin treatment induced a significant elevation of aspartate amino transferase (3.38±5.68 vs -1.15±4.32 UI/L, P

Objectives This study aimed to evaluate the impact of two creatinine measurement methods on the Model for End Stage Liver Disease (MELD) score and glomerular filtration rate estimation (eGFR) in cirrhotic patients. We focused on ID-MS traceable method such as compensated Jaffe (cJafCreat) and enzymatic (EnzCreat) methods. Design and methods Potential protein-related interferences in creatinine determination were evaluated using dialysates spiked with albumin. MELD score, CKD-EPI formula creatinine-based eGFR and cystatin C-based eGFR were evaluated in 100 cirrhotic patients. Results In vitro model demonstrated that low protein levels result in an underestimation of creatinine levels using cJafCreat. In patients, cJafCreat created a negative bias of − 6.1 μmol/L that led to higher eGFR and lower MELD scores. Conclusions cJafCreat contributes to an overestimation of renal function in cirrhotic patients and may alter cirrhosis-severity assessment. Compensated Jaffe assays should therefore be replaced by enzymatic methods.

Objectives We compared automated capillary electrophoresis (CE) systems Capillarys 2® from Sebia and V8® from Helena Biosciences Europe (Elitech) with the semi-automated Hydrasys-Hyrys® agarose gel electrophoresis (AGE) from Sebia. Design and methods We evaluated analytical performances and compared 129 fresh routine sera (group A) to 164 frozen pathologic samples with suspicion or antecedent of monoclonal component (MC) (group B). Immunofixation was then compared with immunotyping provided by both CE systems. Results Analytical performances from both CE systems have proven suitable results for clinical use, with within-run and between-run coefficients of variation inferior or equal to 5.2% and 7.7%, respectively. A good correlation was found between AGE and CE with r-value ranging from 0.81 to 0.96 for both CE systems. We observed high MC detection sensitivities (> 85%) of in electrophoretogram readings for both CE systems. MC identification using CE systems provided suitable concordance with immunofixation, although failing to detect some IgM proteins or free light chains. Conclusions Both Capillarys 2® and V8® are reliable automated CE systems for patient care.

Chronic kidney disease definition is based on glomerular filtration rate (GFR) estimations which are derived from creatinine-based equations. The accuracy of GFR estimation is thus largely dependent of those of serum creatinine assays. International recommendations highlight the need for traceable creatinine assays. The French Society of Clinical Biochemistry conducted a study for measuring accuracy of creatinine enzymatic methods. This evaluation involved 25 clinical laboratories. Creatinine was measured in serum pools ranging from 35.9±0.9 μmol/L to 174.5±3.1 μmol/L (IDMS determination) using 12 creatinine enzymatic methods. For all creatinine values greater than 74.4±1.4 μmol/L, the bias and imprecision did not exceed 5% and 5.9%, respectively. For the lowest value (35.9±0.9 μmol/L), the bias ranged from -1.8 to 9.9% (with one exception). At this level, the imprecision ranged from 1.9 to 7.8%. The true performances of the assays (couples of bias and relative standard deviation), were evaluated using Monte-Carlo simulations. Most of the assays fall within the maximum Total Error of 12% at all concentrations. This study demonstrates substantial improvements in the calibration, traceability and precision of the enzymatic methods, reaching the NKDEP recommendations. Moreover, most of these assays allowed accurate creatinine measurements for creatinine levels lower than 40 μmol/L.

L’obesite se developpe rapidement en Afrique sub-saharienne, particulierement en milieu urbain. Afin d’evaluer les risques que cela pourrait representer pour la sante dans cette region du monde, nous avons etudie les relations entre variables anthropometriques et facteurs de risque cardio-metabolique, dans un echantillon de 166 adultes senegalais vivant a Dakar ou a Thies (âge moyen : 43,2 ± 9,4 ans), selectionnes lors de visites a domicile systematiques. Les resultats montrent que l’obesite est encore rare chez les hommes (3,4 %), mais frequente chez les femmes (29,2 %). Cependant, les femmes ont un rapport taille sur hanches plus bas et un meilleur profil cardio-metabolique que les hommes. L’analyse des relations entre variables anthropometriques et facteurs de risque cardio-metabolique montre qu’elles sont un peu differentes de celles decrites dans les populations caucasiennes, mais elles existent, ce qui doit inciter a ne pas negliger la prevention de l’obesite en Afrique sub-saharienne.

The aim of this study was to analyze the relationship between anthropometric characteristics and cardiometabolic risk factors in urban-dwelling adults in Senegal to evaluate future threats to the public health in terms of chronic diseases.Age- and gender-matched control subjects for a study on the prevalence of lipodystrophy in HIV+ patients were selected between June and September 2006 from the general population through systematic home visits guided by area of residence of cases. After consenting to participate, these subjects underwent anthropometric, clinical and biological examinations in their homes.The sample included 60 men and 106 women, mean age of 43.2 ± 9.4 years. Although the prevalence of overweight and obesity was much higher in women (30.2 and 29.2%, respectively) vs. 23.3 and 3.4%, respectively, in men (P0.001), the women had lower waist-to-hip ratios (mean [95% CI]: 0.78 [0.77-0.80] vs. 0.86 [0.84-0.88] in men; P10(-4)) and better systolic blood pressure, triglyceride and high-density lipoprotein (HDL)-cholesterol levels. However, their insulin levels were significantly higher (32.1 [28.2-36.5] pmol/l vs. 25.5 [21.0-30.8] in men; P0.04). Principal component analysis showed that glucose and insulin correlated with subcutaneous fat, whereas blood pressure correlated with central fat distribution. Lipids were distributed between these two factors.Obesity still appears to be rare in Senegalese urban-dwelling men, whereas women, despite their overweight, have no untoward cardiometabolic profiles. However, the observed correlations between cardiometabolic risk factors and the amount and/or distribution of body fat suggest that obesity prevention should not be overlooked in the public health agenda for sub-Saharan Africa.

The relationship between bone mass and muscle mass may be due to the site-specific effects of loading on bone in adults and to lifestyle, nutritional, and hormonal factors. Another hypothesis is that the maintenance with aging of both appendicular muscle and bone mass may be determined by factors independent of all these previous factors, including genetic factors. In 160 healthy men aged 20 to 72years, we recorded femoral neck bone mineral density (FN BMD), relative appendicular skeletal muscle mass [RASM; appendicular skeletal muscle mass (kg)/height (cm)], age, body mass, maximum grip and knee extension strength, lifetime physical activities, calcium intake, tobacco smoking, and serum parathyroid hormone (PTH), estradiol (E2), free testosterone, dehydroepiandrosterone sulphate (DHEAS), insulin-like growth factor (IGF-I), sex hormone-binding globulin (SHBG), calcium, 25(OH) vitamin D, albumin, and creatinine clearance. The correlation between FN BMD and RASM (that includes upper and lower limb muscle mass) was of slightly greater magnitude than that between FN BMD and the relative upper limb muscle mass and between FN BMD and the relative leg muscle mass (r=0.39; p< or =0.001 versus r=0.36; p< or =0.001 and r=0.34; p< or =0.001, respectively). The stepwise multiple linear regression model showed that FN BMD was significantly associated with RASM (15% of FN BMD variance, p

Introduction Heart failure is the most frequent cardiac complication of chronic kidney disease (CKD). Biomarkers can help identifying high-risk patients. Natriuretic peptides are largely used for monitoring patients with cardiac failure, but are highly dependent of GFR. Soluble suppressor of tumorigenicity 2 (sST2) is identified in risk stratification of cardiovascular events (CVE) in heart failure. Furthermore, sST2 could be included in a bioclinical score to stratify mortality risk. Objective The aim of this study is to evaluate the interest of circulating sST2 level in heart dysfunction, the bioclinical score to predict risk of composite outcome (major adverse coronary events) as well as mortality prediction for CKD patients. Methods A retrospective study was carried out on 214 patients enrolled from 2004 to 2015 at Montpellier University Hospital. sST2 was measured with Presage ST2® kit. CKD status was defined by the CKD-epi equation to estimate GFR. Indices of cardiac parameters were performed by cardiac echography. Results No patient had reduced ejection fraction. 109 patients had left ventricular hypertrophy, and 181 had diastolic dysfunction, with structural, functional abnormalities or both. sST2 is independent of age and eGFR (P = 0.44, r = 0.05 and P = 0.3, r = 0.07, respectively). Regarding echocardiogram data, sST2 is correlated with left ventricular mass index (P = 0.02, r = 0.16), left atrial diameter (P = 0.04, r = 0.14) and volume index (P = 0.05, r = 0.13) and). sST2 alone does not change risk prediction of death and/or CVE compared to cardiac biomarkers. Included in a bio-clinical score sST2 has added value and better stratifies the risk of CVE and/or death in CKD patients. Conclusion sST2 is associated with cardiac remodeling independently of eGFR, unlike other cardiac biomarkers (hs-cTnT and NT-proBNP). Included in a bioclinical score, it allows a better risk stratification of death and/or CVE in early stages of CKD patients.

Introduction Micro-vascular occlusion (MVO) in myocardial infarction (MI) is associated with an increased risk of heart failure and mortality. Our team found that T hs-Troponin has a double peak kinetic after MI. The goal was to determine if this kinetic was correlated to microvascular occlusion evaluated by cardiac magnetic resonance imaging (MRI) after myocardial infarction. Methods This is a monocentric retrospective study. The inclusion criterions were: hospitalization for myocardial infarction, a 0 or 1 TIMI flow, a reperfusion within 12 h from the onset of chest pain, a cardiac MRI within the first month after MI, and a 5 days’ biological follow up with at least hs-T-Troponin and CRP. Statistics were performed using the R software. MRI analysis was blinded to biological analysis. Results Ninety-eight patients were included (82.6% of male, a mean age of 58.9 y.o, 25.6% of diabetes mellitus, 65.3% of dyslipidemia and 50.8% of hypertension). The mean delay from chest pain to angioplasty was 3.5 hours. MI were mostly anterior STEMIs (69.4%). A total of 54.1% of the patients had MVO at MRI. These patients had more frequent dyslipidemia (P = 0.006), lower LVEF on MRI (41.8% (10.0%) vs. 53.5% (11.7%), P Fig. 1 ). Conclusion A second peak highlighted by daily hs-T-Troponin dosage was associated to MVO on MRI after reperfused myocardial infarction in our population. Prospective study in larger population is needed to confirm this observation.

We prospectively assessed the evolution of coronary artery calcification (CAC) and osteoprotegerin (OPG) levels after renal transplantation (RT). Eighty-three recipients were followed-up prospectively during 1 year. Blood was collected before (baseline) and after RT for determination of mineral metabolism parameters including OPG. CAC was measured by multidetector computed tomography at transplantation (baseline) and 1 year later. Progression of CAC was defined as a difference between the follow-up square-root transformed volume (SRV) and the baseline SRV >or= 2.5. By multivariate analysis, baseline OPG level, age and low LDL levels were significantly associated with baseline CAC. RT was accompanied by mineral metabolism improvement with a decrease of OPG from 955 [395-5652] to 527 [217-1818] pg/mL and parathyroid hormone from 94 [1-550] to 62 [16-410] pg/mL. Thirty-one percent of patients did not exhibit CAC at baseline. CAC diminished in 14.5%, stabilized in 59.2% and progressed in 26.3% of patients. Baseline CAC was associated with progression (OR 2.92 [1.02-8.36]). No significant association was found between OPG and CAC progression despite a higher baseline OPG level in progressors (1046 [456-3285]) vs. non-progressors (899 [396-5952] pg/mL). CAC at baseline, but not 1 year after RT, is independently associated with baseline OPG; posttransplant CAC progression is predicted by baseline CAC score.

Le systeme RANKL (receptor activator of nuclear factor kappaB ligand)/RANK/OPG (osteoprotegerine), acteur essentiel du controle de la mineralisation osseuse, est egalement exprime et regule dans les vaisseaux. Il pourrait jouer un role cle a ce niveau en controlant le developpement des calcifications vasculaires. Au-dela de ce role, l’OPG pourrait egalement participer a l’inflammation et a la rupture des plaques d’atherome. Les donnees cliniques montrent qu’elle est egalement un marqueur independant de pathologie vasculaire et du risque cardiovasculaire, notamment chez les patients diabetiques. Dans cette revue, nous faisons le point sur l’implication du systeme RANKL/RANK/OPG dans les calcifications vasculaires et sur le role potentiel de l’OPG en tant que marqueur de risque cardiovasculaire dans la population diabetique.

Oxidative stress is commonly observed in the elderly and could be involved in age-related diseases. However, the determinants of superoxide anion overproduction are not clearly understood. Superoxide anion production was evaluated using a lucigenin-based chemiluminescence method in 478 elderly subjects (304 women, 174 men; 79.5+/-7.1 years). Homocysteine (HCy) metabolism (homocysteinemia, vitamin B12, plasma, and erythrocyte folates), inflammation (CRP, fibrinogen, alpha-1 acid glycoprotein), lipid parameters (total cholesterol, triglycerides, HDL and LDL cholesterol), and nutritional parameters (albumin, transthyretin) were determined. The results show that HCy levels (p0.001) and superoxide anion production (p=0.04) increase with aging, but CRP does not. Highest HCy (20 microM) (OR 1.83 (1.09-3.07), p=0.02) and CRP over 5 mg/L (adjusted OR 2.01 (1.15-3.51), p=0.01) are the main determinants in superoxide anion production in the elderly. These clinical data are confirmed in an in vitro study using THP-1 monocyte-like cells. Incubation with HCy thiolactone (HTL) (0-200 microM) and LPS (0-20 ng/ml) dramatically enhances NADPH oxidase expression and activation. Moreover, a synergic action was evidenced for low concentrations of HTL (20 microM) and LPS (5 ng). Taken together, the clinical data and in vitro experiments support the hypothesis that moderate homocysteinemia and low-grade inflammation synergically enhance NADPH oxidase activity in the elderly.

Resume Les calcifications vasculaires sont un facteur de risque de mortalite important chez les patients insuffisants renaux chroniques. La meilleure connaissance des phenomenes physiopathologiques responsables de la mineralisation vasculaire permet d’envisager l’emergence de nouveaux marqueurs biologiques de calcifications vasculaires. La presence d’une matrice osseuse dans les arteres calcifiees ainsi que de cellules osteoblastiques demontre que les calcifications vasculaires sont un phenomene actif, puissamment regule. Les cellules musculaires lisses vasculaires ont la possibilite de se transdifferencier en osteoblastes en milieu uremique. Comme pour le metabolisme osseux, le systeme OPG–RANK–RANKL peut apparaitre comme une plaque tournante des calcifications vasculaires. Des resultats convergents indiquent que la determination de l’OPG circulante peut etre un marqueur de calcifications. La calcification de cette matrice osseuse est favorisee par la defaillance du systeme inhibiteur, notamment la matrice Gla proteine et la fetuine-A. Enfin, le FGF-23, marqueur precoce et sensible des anomalies osseuses et minerales chez l’insuffisant renal chronique est un marqueur prometteur.

Isoprostanes are a family of prostaglandin isomers produced from oxidation of polyunsaturated fatty acids through a non-enzymatic free radical-catalyzed mechanism. Quantification of F2-isoprostanes (F2-IsoPs) provides a good index of oxidative stress and allows non-invasive assessment of lipid peroxidation in vivo. Since “interferences peaks” at m/z 573 co-elute with d4-15-F2t-IsoP preferentially used, we propose a new GC–NICI-MS approach to quantify urinary F2-IsoPs by using 4(RS)-F4t-neuroprostane as the internal standard. This method was applied to quantify urinary F2-IsoPs excretion in healthy volunteers and polytraumatized patients. Our results showed a significant increase (p

Background and aim In type 2 diabetes, the interplay between cells and inflammatory mediators up-regulates CD36 expression in macrophages. The aim of this work was to investigate advanced glycation end products (AGE)-induced CD36 expression and its regulation by insulin in aortic vascular smooth muscle cells (VSMCs) from Goto–Kakisaki (GK) rats, a non-obese insulin model of both insulin resistance and type 2 diabetes. The context of overexpression of CD36 in aortas was also evaluated. Methods and results VSMCs were isolated and cultured from the aortas of GK rats and non-diabetic rats. The expression of proteins was evaluated by Western blot. The aortic production of superoxide anion (O 2 ·− ) was measured by luminescence on isolated tissue. AGEs and advanced oxidation protein products (AOPPs) were determined in plasma by fluorescence spectroscopy and spectrophotometry, respectively. AGE receptor (RAGE), NF-κB, and CD36 protein expression as well as O 2 ·− production were higher in GK aortas than in control aortas, and AGEs and AOPPs were higher in GK plasma. In VSMCs from non-diabetic rats, insulin was able to reduce (10nM) or suppress (100nM) the protein overexpression of CD36 induced by AGEs–BSA. In contrast, in VSMCs from GK rats, insulin was unable to reduce AGEs–BSA-induced CD36 overexpression. Conclusions The results suggest an overexpression of CD36 in VSMCs from GK rats and impaired control by insulin. In the context of increased plasma AGEs, aortic RAGE overexpression and increased oxidative stress markers, the data are compatible with an AGEs induced CD36 overexpression in diabetes.

Resume Objectif evaluer le statut en retinol, en alpha-tocopherol et en tocotrienol plasmatique d’une population rurale africaine consommant librement et quotidiennement l’huile de palme brute. Methodes cette etude a porte sur 113 sujets volontaires, âges de 18 a 69 ans, recrutes dans la region de Glanle (57 sujets dont 34 femmes et 23 hommes), et dans la region de Bodou (56 sujets dont 32 hommes et 24 femmes) situees respectivement a l’ouest et au sud de la Cote d’Ivoire. Le retinol, l’alpha-tocopherol (AT), les tocotrienols, le cholesterol total (CT) et les triglycerides (TG) plasmatiques ont ete doses chez ces sujets a jeun. L’index d’alpha-tocopherol (IAT) a ete calcule par le ratio AT/CT+TG. Resultats absence de carence en vitamine A dans les deux groupes. Bien que les concentrations plasmatiques d’alpha-tocopherol ne soient pas differentes entre les deux groupes, l’IAT de Glanle etait significativement plus eleve que celui de Bodou (p Conclusion l’huile de palme brute pourrait etre recommandee pour prevenir la carence en vitamine E et A dans les pays en developpement.

Background Transplant patients have an increased incidence of lymphoproliferative disorders. The development of a sensitive immunoassay for serum free light chain (sFLC) determination has improved the diagnosis of monoclonal gammapathy. However, metabolism of FLC largely depends on renal function which could lead to misinterpretation of results. The aim of this study was to assess polyclonal FLC in kidney transplant recipients in relation to markers of renal function. Materials and methods 97 renal transplant patients (median transplantation follow-up of 2.2 years) were included in this study. Kappa FLC, lambda FLC and cystatin C were measured by particle-enhanced turbidimetric immunoassay (PETIA) using kits from a Binding Site (Birmingham, UK) SPA PLUS ® analyzer. Glomerular filtration rate was measured using urinary clearance of 99m Tc-DTPA and estimated using CKD-EPI creatinine 2009, CKD-EPI cystatin C 2012 and CKD-EPI creatinine–cystatin C 2012. Results Serum kappa FLC was 22.38 [6.39–68.91] mg/L and serum lambda FLC was 15.66 [7.29–50.81] mg/L. Both levels of kappa and lambda were correlated with renal function. Median κ/λ ratio was 1.34 [0.57 to 2.67] leaving 19.6% of renal transplant patients outside the normal reference range [0.26–1.65]. However, using a reference interval normalized by renal function [0.37–3.1], none of our patients was classified as abnormal. Conclusion κ/λ ratio should be cautiously analyzed in renal transplantation and renal function, estimated by creatinine/cystatin C equations should be taken into account.

Background: Low HDL-cholesterol, hypertriglyceridemia (HTG) and occurrence of small dense LDL could be involved in increased cardiovascular risk in HIV-infected patients. This study evaluates the effects of fenofibrate and/or Vitamin E on lipoprotein profile. Design: Thirty-six HIV-positive adults with fasting triglycerides (TGs) ≥2mmol/l and stable antiretroviral therapy (ART) were randomly assigned to receive either micronised fenofibrate (200mg/day) or Vitamin E (500mg/day) for a first period of 3 months and the association of both for an additional 3-month period. Methods and results: Total cholesterol, HDL-C, LDL-C, triglycerides, apoA1, apoB, apoCIII, lipoprotein composition, LDL size and LDL resistance to copper-induced oxidation were determined before initiation of fenofibrate or Vitamin E, and 3 and 6 months thereafter. Three months of fenofibrate treatment results in a significant decrease in triglycerides (−40%), apoCIII (−21%), total cholesterol (−14%), apoB (−17%) levels, non-HDL-C (−17%), TG/apoA1 ratio in HDL (−27%) associated with an increase in HDL-C (+15%) and apoA1 (+11%) levels. Moreover, fenofibrate increases LDL size and enhances LDL resistance to oxidation. Three months of Vitamin E supplementation only improves LDL resistance to oxidation and addition to fenofibrate results in a slightly greater effect. Conclusion: Fenofibrate therapy improves the atherogenic lipid profile in HIV-positive adults with hypertriglyceridemia.

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.

Objectives To evaluate the Sentinel-PETIA cystatin C on Architect c8000® analyzer. Design and methods We assessed analytical performances and clinical relevance by comparison with a reference isotopic method in kidney transplant recipients. Results This assay exhibited reliable precision and was close to the non standardized Siemens-PENIA method. All tested equations allowed reliable assessment of GFR. Conclusions Cystatin C improved GFR determination at the critical level of 60 mL/min/1.73 m². New formulas might be necessary after IFCC standardization.

Expression of antioxidant enzymes (AOE), an important mechanism in the protection against oxidative stress, could be modified by the redox status of the cells. The aim of this project was to evaluate the role of vitamin E deficiency in association with a high-cholesterol diet in the hepatic lipid peroxidation and the expression of AOE. Two groups of 6 male rats were fed with a high-cholesterol or a high-cholesterol vitamin E-deficient diet. All animals were sacrificed at 72 days of treatment. Liver lipid peroxidation index (Malondialdehyde; MDA) and hepatic AOE were evaluated. Total liver RNA was extracted, and the steady state messenger RNA (mRNA) levels of glutathion peroxydase, manganese superoxide dismutase, Cu/Zn superoxide dismutase and catalase were examined by northern blot. After 72 days on the diet, a significant increase in the lipid peroxidation index was observed in the vitamin E deficient group (MDA : 4.45 ± 0.29 nmol/mg protein versus 3.65 ± 0.1 nmol/mg protein in vitamin E normal group). Despite this oxidative stress, the activities and mRNA levels of liver AOE were not significantly different in the 2 groups. These preliminary results show that chronic vitamin E deficiency associated with high cholesterol diet is able to increase lipid peroxidation without modulation of AOE expression and activity in the liver. This suggests that beneficial effects of dietary vitamin E are due to a plasma antioxidant effect or a cell mediated action, rather than to a specific modulation of cellular enzymes.

The use of spline functions in the analysis of empirical two-dimensional (2-D) data (yi, xi) is described. Spline functions are excellent empirical functions, which can be used with advantage instead of other ones, such as polynomials or exponentials. The knot location seen as variable value corresponds to classical parameter used to describe oxidation curves. An application on characterization of LDL oxidability shows free knot splines in a regression context.

Aims: To evaluate if transradial diagnostic coronary angiogram by itself could lead to a systemic inflammation. Methods: In 96 patients with baseline hs-CRP level

Objective Oxidative mechanisms may play an important role in the etiology of cataract and age-related macular degeneration (AMD). The authors present the level of two antioxidant enzymes in relation to cataract and AMD. Design Population-based, cross-sectional study on cataract and AMD and their risk factors. Participants This study includes 2584 participants recruited among the residents of the town of Sete (in the south of France), who were 60 years of age or older. Intervention/methods Cataract was defined on the basis of slit-lamp examination, according to the Lens Opacities Classification System III, and AMD on the basis of fundus photographs according to an international classification. Biologic measurements were made centrally from blood samples for which the patient fasted. Main outcome measures The presence of early and late AMD and of subcapsular, cortical, nuclear, and mixed cataracts was assessed and related to the levels of plasma glutathione peroxidase and erythrocyte superoxide dismutase. Results After multivariate adjustment, higher levels of plasma glutathione peroxidase (plGPx) were significantly associated with a ninefold increase in late AMD prevalence, a sixfold increase in cortical cataract, and a twofold increase in nuclear and mixed cataracts. High levels of erythrocyte superoxide dismutase (SOD) activity were not associated with late AMD and early signs of AMD but were associated with a twofold increase in nuclear cataract. Conclusion The authors show here, for the first time, a strong association of high levels of plGPx with age-related eye diseases. High levels of SOD also are associated with increased risk of nuclear cataract. More data are needed at the biochemical and epidemiologic levels for a better understanding of these findings.

beta(2)M is a strong and independent indicator of hemodialysis patient outcomes and an excellent surrogate for middle molecules, and deserves to be routinely monitored and incorporated into dialysis adequacy targets. beta(2)M has a double meaning, reflecting both dialysis efficacy in terms of solute mass transfer and patient bioactivity. The work of Ward et al. in this issue warrants a study to test the hypothesis that long daily hemodiafiltration treatment would be the optimal renal replacement modality to improve dialysis patient outcomes.

Introduction et but de l’etude Dans le contexte actuel d’epidemie de l’obesite (1), il est essentiel de definir des marqueurs associes a ses complications metaboliques et cardio-vasculaires. L’existence d’une inflammation de bas grade est etablie chez les patients obeses mais les donnees concernant la procalcitonine (PCT), un marqueur habituel de l’inflammation et du sepsis, ont ete peu explorees chez les patients obeses. Pourtant, la PCT peut etre secretee par le tissu adipeux inflammatoire (2). Recemment, il a ete montre qu’elle etait associee aux parametres cliniques, anthropometriques et biologiques d’obesite, du syndrome metabolique et de l’insulinoresistance dans la population generale et dans une cohorte de femmes aux ovaires polykystiques (3, 4). L’objectif de cette etude etait donc d’evaluer la relation entre les concentrations de PCT et les parametres metaboliques en condition d’obesite. Materiel et methodes Tous les patients obeses non diabetiques admis dans le departement de Nutrition et Diabete entre janvier 2010 et decembre 2013 ont beneficie d’une evaluation clinique et metabolique de leur obesite, d’une etude de leur composition corporelle par absorptiometrie biphotonique (DEXA) ainsi qu’un dosage des marqueurs de l’inflammation incluant la PCT. Resultats et Analyse statistique Les parametres anthropometriques et biologiques ont ete divises en terciles tenant compte du sexe. Les concentrations de PCT les plus elevees des 295 patients inclus etaient significativement associees avec le degre d’obesite (OR = 2,76 [1,26–6,03], obesite de classe III vs classe I, p =0,011), le tour de taille (OR = 4,20 [1,98–8,92], 3 e vs 1 er tercile, p e vs 1 er tercile, p =0,001) apres ajustement sur la C-reactive protein ultrasensible. Par ailleurs, aucune association n’ avait ete retrouvee entre les valeurs elevees de PCT et de C-reactive protein ultrasensible (OR = 1,33 [0,68–2,26], p =0,404). De plus, ni la PCT plasmatique (OR = 1,26 [0,67–2,37], p =0,475), ni le tour de taille (OR = 1,91 [0,99–3,70], p =0,053) ou le ratio masse grasse du tronc sur masse grasse totale (OR = 1,09 [0,46–2,58], p =0,840) n’etaient associees a l’insulinoresistance. Conclusion Nos resultats montrent que la PCT plasmatique est un marqueur de l’accumulation de tissu adipeux abdominal, evaluee aussi bien cliniquement que par DEXA, et ce, independamment des autres marqueurs biologiques de l’inflammation. Elle pourrait etre un temoin d’une dysfonction adipocytaire alors meme qu’elle n’est associee ni a l’insulinoresistance, ni au syndrome metabolique dans notre population obese.

To assess the role of superoxide (O2−) and nitric oxide (NO) in ischaemic-reperfusion-induced acute renal failure, we investigated whether an activation of the L-arginine-NO pathway contributes to ischaemia-reperfusion-induced kidney membrane peroxidation by measurement of 4-hydroxynonenal (HNE) content in anaesthetized rats submitted to acute renal ischaemia. Following ischaemia-reperfusion injury, renal blood flow (RBF) was significantly reduced, while renal vascular resistance was significantly increased. Infusion of neither L -arginine nor D -arginine led to a recovery of RBF. L -Arginine, but not D -arginine, caused a significant increase in HNE accumulation in the ischaemic kidney. L -Arginine infusion enhanced the degree of lipid peroxidation afforded by ischaemia-reperfusion injury in the kidney suggesting that products of the endogenous L -arginine-NO pathway may react with O2− to initiate lipid peroxidation.

Objectif Etudier sur un echantillon de 1105 sujets ≥ 65 ans, non dements, non institutionnalises, l’impact des troubles du sommeil sur le declin de la fonction renale sur un suivi de 11 ans. Methodes Le taux de filtration glomerulaire a ete estime a l’inclusion dans l’etude et a 11 ans de suivi. Un declin significatif du debit de filtration glomerulaire (DFG) a ete defini par une reduction de 22 % de l’ecart relatif entre les 2 taux de filtration glomerulaire, correspondant au dernier tertile de la distribution. Les plaintes d’insomnie (difficultes a initier/maintenir le sommeil, reveil matinal precoce) et la somnolence diurne excessive (SDE) ont ete evaluees a l’inclusion par auto-questionnaires. Le syndrome des jambes sans repos (SJSR) et son âge de debut ont ete renseignes a 11 ans de suivi. Un enregistrement polysomnographique a domicile a ete realise (n = 277). L’index d’apnees-hypopnees (IAH), le temps total de sommeil (TTS) et les mouvements periodiques des jambes (MPJ) ont ete retenus. Des modeles de regression logistiques ajustes sur des facteurs de confusion potentiels ont ete menes. Resultats Un risque accru du declin du DFG est associe a la SDE (OR = 1,67, p = 0,003) et au SJSR (OR = 1,98, p = 0,009) independamment des facteurs de risque cardiovasculaires. Parmi les plaintes d’insomnie, seule une association a ete retrouvee avec les reveils precoces (p = 0,05). Un IAH severe et un TTS court sont associes au declin du DFG mais seule l’association avec IAH persiste apres ajustement. Conclusion La SDE, le SJSR et l’IAH constituent des facteurs de risque independant d’un declin du DFG chez le sujet âge.

Introduction La copeptine, marqueur de stress endovasculaire est un outil d’aide au diagnostic d’exclusion precoce de l’infarctus du myocarde sans elevation du segment ST (IDM non ST+). Une etude recente montre que le dosage combinee de troponine et copeptine a l’admission permet le retour a domicile precoce des patients admis aux urgences pour suspicion de syndrome coronarien aigu, et a risque faible et intermediaire (Grace Materiel et methodes Etude observationnelle prospective comparative de type avant-apres menee sur 1 an chez des patients admis aux urgences pour douleurs thoraciques non traumatiques sans elevation du segment ST et datant de moins de 10 h, dans le cadre de la prise en charge courante. En phase I, la prise en charge se fait en aveugle du dosage de la copeptine, realisee a partir d’un prelevement veineux congele a l’admission (Kryptor, ThermoFisher Scientific) (collection biologique DC-2009-1052). En phase II, la prise en charge est basee sur un algorithme decisionnel incluant le dosage de copeptine a l’admission (seuil 14 ng/L) et les facteurs de risque. Les patients a « bas risque » (pas d’antecedent coronarien et un score de GRACE Resultats Au total, 189 patients ont ete inclus, 122 patients presentant un dosage d’hs-cTnT negatif a l’admission ont ete analyses (61 patients dans la phase I et 61 patients dans la phase II, âge : 52 ± 15 ans, sexe masculin 56,6 %). Le taux d’ECM est de 3,8 % (n = 2/53) en phase I et 5,9 % (n = 3/51) en phase II (p = 0,68) pour les patients avec un dosage d’hs-cTnT et copeptine negatif. Aucun ECM n’est observe chez les patients double negatif et a bas risque (n = 42 (79 %) en phase I, n = 41 (80 %) en phase II). Chez ces patients, le nombre de redosage de hs-cTnT a H + 3 est reduit de 45,2 % (n = 19) en phase I a 22 % (n = 9) en phase II (p = 0,025), et le nombre de retour a domicile precoce augmente de 83,3 % (n = 35) en phase I a 92,7 % (n = 38) en phase II (p = 0,31). Discussion Un algorithme de prise en charge des douleurs thoraciques integrant le dosage de la copeptine et les facteurs de risque est fiable et permet un retour a domicile precoce des patients a bas risque de NSTEMI en limitant la repetition des dosages sanguins et le risque d’evenement cardiaque majeur au decours.