Pharmacokinetic characterisation of a valproate Autism Spectrum Disorder rat model in a context of co-exposure to α-Hexabromocyclododecane.

Assessing the role of α-hexabromocyclododecane α-HBCDD as a factor of susceptibility for Autism Spectrum disorders by using valproic acid-exposed rat model (VPA) required characterizing VPA pharmacokinetic in the context of α-HBCDD-co-exposure in non-pregnant and pregnant rats. The animals were exposed to α-HBCDD by gavage (100 ng/kg/day) for 12 days. This was followed by a single intraperitoneal dose of VPA (500 mg/kg) or a daily oral dose of VPA (500 mg/kg) for 3 days. Exposure to α-HBCDD did not affect the pharmacokinetics of VPA in pregnant or non-pregnant rats. Surprisingly, VPA administration altered the pharmacokinetics of α-HBCDD. VPA also triggered higher foetal toxicity and lethality with the PO than IP route. α-HBCDD did not aggravate the embryotoxicity observed with VPA, regardless of the route of exposure. Based on this evidence, a single administration of 500 mg/kg IP is the most suitable VPA model to investigate α-HBCDD co-exposure.

Limited cross reactivity among arginine kinase allergens from mealworm and cricket edible insects.

Insects are seen as a solution to the increasing demand for protein sources for food. However, entomophagy has unfortunately been linked to allergic reactions in Europe with people with professional contacts. As mealworms (Tenebrio molitor) and crickets (Acheta domesticus) have recently become commercially available (both whole or in food formulation) in several European countries, this research assessed the cross allergenicity of arginine kinase (AK). Based on the collection of sera from a entomology laboratory staff, oven cooked insects but also purified AK fractions were tested. Immunoblotting against the protein extracts revealed different Immunoglobulin E reactivity of sera according to the insect target species: two bands (40 and 14 kDa) for crickets and a pattern including light responses at 17, 25 and 37 kDa for mealworms. Focusing on AK, low specific allergenicity was here illustrated and discussed in relation to the development of a safe edible insect consumption by humans.

Impact of rapid microbial identification directly from positive blood cultures using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry on patient management.

For septic patients, delaying the initiation of antimicrobial therapy or choosing an inappropriate antibiotic can considerably worsen their prognosis. This study evaluated the impact of rapid microbial identification (RMI) from positive blood cultures on the management of patients with suspected sepsis. During a 6-month period, RMI by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was performed for all new episodes of bacteraemia. For each patient, the infectious disease specialist was contacted and questioned about his therapeutic decisions made based on the Gram staining and the RMI. This information was collected to evaluate the number of RMIs that led to a therapeutic change or to a modification of the patient's general management (e.g. fast removal of infected catheters). During the study period, 277 new episodes of bacteraemia were recorded. In 71.12% of the cases, MALDI-TOF MS resulted in a successful RMI (197/277). For adult and paediatric patients, 13.38% (21/157) and 2.50% (1/40) of the RMIs, respectively, resulted in modification of the treatment regimen, according to the survey. In many other cases, the MALDI-TOF MS was a helpful tool for infectious disease specialists because it confirmed suspected cases of contamination, especially in the paediatric population (15/40 RMIs, 37.50%), or suggested complementary diagnostic testing. This study emphasizes the benefits of RMI from positive blood cultures. Although the use of this technique represents an extra cost for the laboratory, RMI using MALDI-TOF MS has been implemented in our daily practice.

Anti-cyclic citrullinated peptide antibodies: a comparison of different assays for the diagnosis of rheumatoid arthritis.

OBJECTIVES: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific markers of rheumatoid arthritis (RA). Considering the heterogeneity of the target antigens involved, and the test platforms and conjugates proposed in commercial anti-CCP assays, we assessed the diagnostic performances of four fully automated anti-CCP assays in a cohort of patients with RA compared to patients with other autoimmune and inflammatory disorders. We also evaluated the agreement between the qualitative results of these immunoassays. METHOD: We evaluated three anti-CCP2 assays [Eurodiagnostica enzyme-linked immunosorbent assay (ELISA), Elecsys electrochemiluminescence immunoassay (ECLIA) on the Modular E170 Analyzer, and Zenit chemiluminescence immunoassay (CLIA) on the Zenit RA Analyzer] and one anti-CCP3 assay (Inova ELISA). ELISAs were performed on an automated workstation. Samples from 112 patients with RA and a disease control group of 136 patients (53 with autoimmune diseases, 65 non-autoimmune disorders, and 18 infectious diseases) were studied (included 161 samples submitted consecutively to the laboratory). RESULTS: At a fixed specificity of 92%, the anti-CCP3 assay presented the highest sensitivity (75%) compared to the anti-CCP2 assays evaluated (63-72%). The Zenit anti-CCP2 assay gave the most false-positive results (especially in patients with viral infections and connective tissue diseases). The agreement between assays ranged from 86.3% to 95.2% and Kappa coefficients ranged from 0.724 to 0.899. CONCLUSIONS: Recently released automated workstations provide a valuable alternative to ELISA to diagnose RA. However, differences in diagnostic performances are highlighted in our experience, especially for the Zenit assay. In our cohort, the anti-CCP3 assay gave slightly better performances than the anti-CCP2 assays (with the exception of the Zenit assay).

An automated chemiluminescence immunoassay may detect mostly relevant IgG anticardiolipin antibodies according to revised Sydney criteria.

BACKGROUND: Detection of anticardiolipin antibodies (ACA) is an independent laboratory criterion for diagnosis of antiphospholipid syndrome (APS). Alternative methods to ELISA were recently developed such as automated chemiluminescence immunoassay (CLIA). PATIENTS AND METHODS: We compared a CLIA to an ELISA kit for the detection of IgG isotype of ACA. 87 routine samples from 75 patients suspected of having APS were tested using each method. Cut-off values were calculated in our laboratory for each test using 99th percentile of 50 normal controls. RESULTS: Cut-off values were >20 GPL for ELISA and > 2 GPL for CLIA. Overall agreement (OA), agreement for positive (AP) and agreement for negative (AN) cases were 56.3%, 49.2% and 77.2% respectively. Most discrepant results were positive with ELISA and negative with CLIA. However, OA, AP and AN increased to 82.1%, 84.6% and 80% respectively when CLIA was compared to the repeated ELISA performed at least 12 weeks later. When correlated with APS-related clinical background, CLIA showed lower sensitivity, higher specificity and higher likelihood ratio (LR) as compared to first ELISA whereas these parameters were similar to those of the repeated ELISA. No association was found between any test results and APS-related clinical background of the patients. Using our own cut-off value (> 2GPL), sensitivity, specificity and LR of CLIA to identify patients with APS were respectively 100%, 72.3% and 3.6. A ROC curve showed that at 7.5 GPL cut-off value, specificity and LR improved to 91.1% and 11.25 respectively, without affecting sensitivity. A strong correlation was observed between CLIA results and APS (Chi2 = 12.25; p < 0.001). CONCLUSION: The performance of CLIA is as good as a repeated ELISA test to detect IgG ACA in suspected APS patients. It is fully automated, which represents several advantages over semi-manual ELISA techniques for its implementation in a routine laboratory.

[Thrombin generation test: establishment of reference values according to age and tissue factor concentration is essential before implementation into the laboratory]. / Test de génération de thrombine: importance d'établir les valeurs de référence en fonction de l'âge et des concentrations en facteur tissulaire avant l'implémentation au laboratoire.

The calibrated and automated thrombinography (CAT) developed by H.C. Hemker is a simple and reproducible technique that can be potentially used in coagulation laboratories. This test is able to record the complete thrombin generation in vitro, giving an interesting approach in the evaluation of the haemostatic potential at the individual level. We aimed to implement this test in our laboratory to follow patients with haemorrhagic or thrombotic pathologies. Haemorrhagic and thrombotic disorders are incompletely explored by the coagulation tests used presently in routine labs. These tests don't indeed reflect the real haemostatic phenotype of the patient neither the individual response to haemostatic treatments. Furthermore, they don't have any predictive value for the occurrence of haemorrhage and/or thrombosis. We report here reference values we established in a population of children and adults in pre-analytical conditions easily applicable in coagulation labs. Platelet poor plasma is prepared by a double centrifugation and analyzed immediately or frozen at -80 degrees C for delayed analysis.