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University of Technology of Compiègne, France

Gillery P.,University Hospital of Reims
Journal of Medical Biochemistry | Year: 2011

During their biological life, proteins are exposed in a cumulative way to irreversible nonenzymatic post-translational modifications that are responsible for their molecular aging and generate specific by-products called post-translational modification derived products (PTMDPs). PTMDPs are involved in the pathogenesis of various diseases such as diabetes mellitus, renal insufficiency and atherosclerosis, and are potential biomarkers in clinical practice. Nonenzymatic glycation refers to the spontaneous binding of glucose and reducing sugars to free amino groups and is amplified by oxidative processes (referred to as «glycoxidation»). It generates many reactive by-products such as aldehydes and leads to the formation of «advanced glycation end products» (AGEs). AGEs accumulate in vivo, alter tissue organization and activate membrane receptors such as RAGE, which triggers inflammatory responses. Carbamylation is due to the binding of isocyanic acid, formed in vivo either by spontaneous dissociation of urea or by action of myeloperoxidase on thiocyanate, and generates homocitrulline from lysine groups. Carbamylation leads to alteration of the structural and biological properties of proteins, and favors inflammation and atherosclerosis. PTMDPs may be assayed by different methods, among others LC-MS/MS or immuno assays, constitute a promising field of investigation in basic research and are potential major biomarkers in laboratory medicine.

Deslee G.,University Hospital of Reims | Klooster K.,University of Groningen | Hetzel M.,Krankenhaus Vom Roten Kreuz | Stanzel F.,Lungenklinik | And 9 more authors.
Thorax | Year: 2014

Background: The lung volume reduction (LVR) coil is a minimally invasive bronchoscopic nitinol device designed to reduce hyperinflation and improve elastic recoil in severe emphysema. We investigated the feasibility, safety and efficacy of LVR coil treatment in a prospective multicentre cohort trial in patients with severe emphysema. Methods: Patients were treated in 11 centres. Safety was evaluated by recording all adverse events, efficacy by the St George's Respiratory Questionnaire (SGRQ) as primary endpoint, and pulmonary function testing, modified Medical Research Council dyspnoea score (mMRC) and 6-min walk distance (6MWD) up to 12 months after the final treatment. Results: Sixty patients (60.9 ± 7.5 years, forced expiratory volume in 1 s (FEV1) 30.2 ± 6.3% pred) were bronchoscopically treated with coils (55 bilateral, 5 unilateral), with a median of 10 (range 5-15) coils per lobe. Within 30 days post-treatment, seven chronic obstructive pulmonary disease exacerbations (6.1%), six pneumonias (5.2%), four pneumothoraces (3.5%) and one haemoptysis (0.9%) occurred as serious adverse events. At 6 and 12 months, respectively, ΔSGRQ was -12.1±12.9 and -11.1±13.3 points, Δ6MWD was +29.7±74.1 m and +51.4±76 m, ΔFEV1was +0.11 ±0.20 L and +0.11±0.30 L, and ΔRV (residual volume) was -0.65±0.90 L and -0.71±0.81 L (all p<0.01). Post hoc analyses showed significant responses for SGRQ, 6MWD and RV in patients with both heterogeneous and homogeneous emphysema. Conclusions: LVR coil treatment results in significant clinical improvements in patients with severe emphysema, with a good safety profile and sustained results for up to 1 year. Trial registration number: NCT01328899. © 2014, BMJ Publishing Group. All rights reserved.

Barbaud A.,University of Lorraine | Collet E.,University Hospital of Dijon | Milpied B.,University Hospital of Bordeaux | Assier H.,University Henri Mondor Hospital | And 9 more authors.
British Journal of Dermatology | Year: 2013

Background Drug patch tests (PTs) can reproduce delayed hypersensitivity to drugs and entail a moderate re-exposure of patients to offending drugs. Objectives To determine the value of PTs for identifying the responsible drug in severe cutaneous adverse drug reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Methods In a multicentre study, PTs were conducted on patients referred for DRESS, AGEP or SJS/TEN within 1 year of their SCAR. All drugs administered in the 2 months prior to and the week following the onset of the SCAR were tested. Results Among the 134 patients included (48 male, 86 female; mean age 51.7 years), positive drug PTs were obtained for 24 different drugs. These included positive tests for 64% (46/72) of patients with DRESS, 58% (26/45) of those with AGEP and 24% (4/17) of those with SJS/TEN, with only one relapse of AGEP. The value of PTs depended on the type of drug and the type of SCAR (e.g. carbamazepine was positive in 11/13 DRESS cases but none of the five SJS/TEN cases). PTs were frequently positive for beta lactams (22 cases), pristinamycin (11 cases) and in DRESS with pump proton inhibitors (five cases), but were usually negative for allopurinol and salazopyrin. Of 18 patients with DRESS, eight had virus reactivation and positive PTs. In DRESS, multiple drug reactivity was frequent (18% of cases), with patients remaining sensitized many years later. Conclusions PTs are useful and safe for identifying agents inducing SCAR. © 2012 British Association of Dermatologists.

Gillery P.,University Hospital of Reims | Gillery P.,French National Center for Scientific Research | Jaisson S.,University Hospital of Reims | Jaisson S.,French National Center for Scientific Research
Journal of Proteomics | Year: 2013

Molecular aging of proteins results from the complex association of different reactions that lead to the progressive alteration of their structural and functional properties. These reactions, which include oxidation, glycoxidation, carbonylation and carbamylation, occur during aging and are amplified in various chronic diseases such as diabetes or chronic renal failure. Specific compounds generated throughout this process called post-translational modification derived products (PTMDPs) have been suggested to be promising biomarkers for the management of chronic diseases. During the last decades, the emergence of mass spectrometry and proteomics has largely contributed to the development of sensitive and specific analytical methods devoted to PTMDP quantification in biological fluids. This review aimed at providing evidences for the clinical relevance of PTMDPs as biomarkers in chronic diseases, and at emphasizing on the contribution of mass spectrometric and proteomic methods in this field. Different issues that should be addressed in order to ensure the implementation of these biomarkers in clinical practice have been highlighted.This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine. © 2013 Elsevier B.V.

Fauvet R.,University of Picardie Jules Verne | Brzakowski M.,University of Picardie Jules Verne | Morice P.,University Paris - Sud | Resch B.,University of Rouen | And 3 more authors.
Annals of Oncology | Year: 2012

Background: The purpose of the current study was to evaluate the characteristics of borderline ovarian tumors (BOTs) diagnosed during pregnancy. Patients and methods: We conducted a retrospective multicenter study of 40 patients with BOTs diagnosed during pregnancy between 1997 and 2009 at five tertiary universitary departments of Gynecology and Obstetrics and one French cancer center. The medical records were reviewed to determine surgical procedure, histology, restaging surgery and recurrence. Results: Mean patient age was 30.2 ± 5.4 years. Most BOTs were diagnosed during the first trimester of pregnancy (62%). Salpingo-oophorectomy (N = 24) was more frequently performed than cystectomy (N = 11) during pregnancy (P = 0.01). Only two patients had an initial complete staging. BOTs were mucinous, serous and mixed in 48%, 42% and 10% of patients, respectively. Twenty-one percent of mucinous BOTs exhibited intraepithelial carcinoma or microinvasion. Forty-seven percent of serous BOTs exhibited micropapillary features, noninvasive implants or microinvasion. Restaging surgery performed in 52% patients resulted in upstaging in 24% of cases. Recurrence rate in patients with serous BOT with micropapillary features or peritoneal implants was 7.5%. Conclusions: BOTsdiagnosedduringpregnancy exhibit a highincidence of aggressive featuresand are rarely completely staged initially. Given this setting, up-front salpingo-oophorectomy should be considered and restaging planned. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

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