Comparison of two enzymatic immunoassays, high resolution mass spectrometry method and radioimmunoassay for the quantification of human plasma histamine

International audienceHistamine (HA) is one of the main immediate mediators involved in allergic reactions. HA plasma concentration is well correlated with the severity of vascular and respiratory signs of anaphylaxis. Consequently, plasma quantification of HA is useful to comfort the diagnosis of anaphylaxis. Currently, radioimmunoassay (RIA) is the gold standard method to quantify HA due to its high sensitivity, but it is time consuming, implicates specific formations and cautions for technicians, and produces hazardous radioactive wastes. The aim of this study was to compare two enzymatic immunoassays (EIA) and one in-house liquid chromatography high-resolution mass spectrometry method (LC-HRMS) with the gold standard method for HA quantification in plasma samples of patients suspected of anaphylaxis reactions. Ninety-two plasma samples were tested with the 4 methods (RIA, 2 EIA and LC-HRMS) for HA quantification. Fifty-eight samples displayed HA concentrations above the positive cut-off of 10 nM evaluated by RIA, including 18 highly positive samples (>100 nM). Our results showed that Immunotech® EIA and LC-HRMS concentrations were highly correlated with RIA values, in particular for samples with a HA concentration around the positive cut-off. In our hands, plasma concentrations obtained with the Demeditec Diagnostics® EIA correlated less with results obtained by RIA, and an underestimation of plasma HA levels led to a lack of sensitivity. In conclusion, this study demonstrates that Immunotech® EIA and LC-HRMS method could be used instead of RIA to assess plasma HA in human diagnostic use

Economy-wide effects of coastal flooding due to sea level rise: A multi-model simultaneous treatment of mitigation, adaptation, and residual impacts

This article presents a multi-model assessment of the macroeconomic impacts of coastal flooding due to sea level rise and the respective economy-wide implications of adaptation measures for two greenhouse gas (GHG) concentration targets, namely the Representative Concentration Pathways (RCP)2.6 and RCP4.5, and subsequent temperature increases. We combine our analysis, focusing on the global level, as well as on individual G20 countries, with the corresponding stylized RCP mitigation efforts in order to understand the implications of interactions across mitigation, adaptation and sea level rise on a macroeconomic level. Our global results indicate that until the middle of this century, differences in macroeconomic impacts between the two climatic scenarios are small, but increase substantially towards the end of the century. Moreover, direct economic impacts can be partially absorbed by substitution effects in production processes and via international trade effects until 2050. By 2100 however, we find that this dynamic no longer holds and economy-wide effects become even larger than direct impacts. The disturbances of mitigation efforts to the overall economy may in some regions and for some scenarios lead to a counterintuitive result, namely to GDP losses that are higher in RCP26 than in RCP45, despite higher direct coastal damages in the latter scenario. Within the G20, our results indicate that China, India and Canada will experience the highest macroeconomic impacts, in line with the respective direct climatic impacts, with the two first large economies undertaking the highest mitigation efforts in a cost-efficient global climate action. A sensitivity analysis of varying socioeconomic assumptions highlights the role of climate-resilient development as a crucial complement to mitigation and adaptation efforts

Eptifibatide provides additional platelet inhibition in Non–ST-Elevation myocardial infarction patients already treated with aspirin and clopidogrel Results of the platelet activity extinction in Non–Q-Wave myocardial infarction with aspirin, clopidogrel, and eptifibatide (PEACE) study

AbstractObjectivesThe present study hypothesis was that eptifibatide offered further antiplatelet efficacy above clopidogrel in non–ST-elevation myocardial infarction (NSTEMI) patients before an expeditive coronary intervention.BackgroundAlthough thienopyridines and glycoprotein (GP) IIb/IIIa antagonists are often co-prescribed in the context of NSTEMI, the antiplatelet interaction of these agents is poorly described and the superiority of GP IIb/IIIa antagonists above thienopyridine treatment alone is not clear.MethodsThirty-two NSTEMI patients treated with aspirin and enoxaparin were studied using flow cytometry to define parameters of platelet activation with a panel of agonists before clopidogrel, after clopidogrel, and during an eptifibatide infusion following the clopidogrel load.ResultsAfter platelet activation with adenosine diphosphate, thrombin receptor-activating peptide, or U46-619, relative reductions in conformationally activated GP IIb/IIIa receptor expression (evaluated with PAC-1) of 48%, 43%, and 33%, respectively (all p < 0.0001), were seen with clopidogrel, but further 80%, 78%, and 72% (all p < 0.0001) reductions were seen with eptifibatide. With the same agonists, fibrinogen binding was significantly reduced after clopidogrel by 70%, 64%, and 81% (all p < 0.0001) and again further reduced with eptifibatide by 90%, 95%, and 69% (all p < 0.0001). The total number of GP IIb/IIIa receptors (measured as P2 expression) and P-selectin expression fell after clopidogrel, after ex vivo stimulation with the same agonists; however, both parameters increased slightly during the eptifibatide infusion.ConclusionsThe activated GP IIb/IIIa expression and fibrinogen binding findings indicate that eptifibatide provides significant potent antiplatelet activity above aspirin and clopidogrel, suggesting additive immediate protection in the treatment of NSTEMI. The P2 and P-selectin findings suggest the possibility of a partial agonist and/or pro-inflammatory effect

Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III

Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12–/– mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes

Growth, Productivity, Biomass and Carbon Stock in Eucalyptus saligna and Grevillea robusta Plantations in North Kivu, Democratic Republic of the Congo

peer reviewedInitiated by the World Wildlife Fund (WWF) more than a decade ago in North Kivu, sin- gle-species plantations of Eucalyptus saligna and Grevillea robusta constitute, with other village plantations, the current legal source of wood-energy for the communities bordering the Virunga National Park (PNVi). This study assesses the growth and productivity of these plantations in two sites with different soil and climatic conditions to predict their production over time. The study also assesses the carbon stock and long-term CO2 fixation in the biomass of the studied plantations to deduce their contribution to climate change mitigation. Non-destructive inventories were carried out during three consecutive years in 20 E. saligna and 12 G. robusta plantations in Sake and Kirumba. Analysis of the data revealed that both species have similar diametric growth while height growth and productivity were significantly higher in the E. saligna plantations. The productivity of E. saligna was also higher in Kirumba than in Sake, while that of G. robusta was higher in Sake than in Kirumba. The differences observed were mainly related to species, silviculture, altitude and concentration of bioavailable elements in the soils. The analysis of productivity evolution over time allowed us to determine optimal rotations at 8 and 12 years, respectively, for E. saligna and G. robusta plantations. The relationships between biomass or carbon stock and tree diameter were not different between the studied species but were significantly different at the stand level. If silviculture was standardized and plantations carefully monitored, carbon stock and long-term CO2 fixation would be higher in G. robusta plantations than in E. saligna plantations. These results indicate that while for productivity reasons E. saligna is the favoured species in wood-energy plantations to quickly meet the demand of the growing and disadvantaged population living in the vicinity of PNVi, carefully monitored G. robusta plantations could be more interesting in terms of carbon credits. To simultaneously optimise wood-energy production and carbon storage in the plantations initiated in North Kivu, E. saligna and G. robusta should be planted in mixture. In addition, species and site characteristics adapted silvicultural management practices must be applied to these plantations, which are very important for the region, its population and its park. Finally, the economic profitability as well as the sustainability of the plantations should be assessed in the longer term in North Kivu