Inflammatory Potential of Four Different Phases of Calcium Pyrophosphate Relies on NF-κB Activation and MAPK Pathways

Background: Calcium pyrophosphate (CPP) microcrystal deposition is associated with wide clinical phenotypes, including acute and chronic arthritis, that are interleukin 1β (IL-1β)-driven. Two CPP microcrystals, namely monoclinic and triclinic CPP dihydrates (m- and t-CPPD), have been identified in human tissues in different proportions according to clinical features. m-CPP tetrahydrate beta (m-CPPTβ) and amorphous CPP (a-CPP) phases are considered as m- and t-CPPD crystal precursors in vitro.Objectives: We aimed to decipher the inflammatory properties of the three crystalline phases and one amorphous CPP phase and the intracellular pathways involved.Methods: The four synthesized CPP phases and monosodium urate crystals (MSU, as a control) were used in vitro to stimulate the human monocytic leukemia THP-1 cell line or bone marrow-derived macrophages (BMDM) isolated from WT or NLRP3 KO mice. The gene expression of pro- and anti-inflammatory cytokines was evaluated by quantitative PCR; IL-1β, IL-6 and IL-8 production by ELISA; and mitogen-activated protein kinase (MAPK) activation by immunoblot analysis. NF-κB activation was determined in THP-1 cells containing a reporter plasmid. In vivo, the inflammatory potential of CPP phases was assessed with the murine air pouch model via cell analysis and production of IL-1β and CXCL1 in the exudate. The role of NF-κB was determined by a pharmacological approach, both in vivo and in vitro.Results:In vitro, IL-1β production induced by m- and t-CPPD and m-CPPTβ crystals was NLRP3 inflammasome dependent. m-CPPD crystals were the most inflammatory by inducing a faster and higher production and gene expression of IL-1β, IL-6, and IL-8 than t-CPPD, m-CPPTβ and MSU crystals. The a-CPP phase did not show an inflammatory property. Accordingly, m-CPPD crystals led to stronger activation of NF-κB, p38, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) MAPKs. Inhibition of NF-κB completely abrogated IL-1β and IL-8 synthesis and secretion induced by all CPP crystals. Also, inhibition of JNK and ERK1/2 MAPKs decreased both IL-1β secretion and NF-κB activation induced by CPP crystals. In vivo, IL-1β and CXCL1 production and neutrophil infiltration induced by m-CPPD crystals were greatly decreased by NF-κB inhibitor treatment.Conclusion: Our results suggest that the inflammatory potential of different CPP crystals relies on their ability to activate the MAPK-dependent NF-κB pathway. Studies are ongoing to investigate the underlying mechanisms

The financial penalty for "unfair" debt: The case of Cuban bonds at the time of independence

Unfair sovereign debts, used, for instance, to suppress a rebellion, may be declared odious and not be repaid once the former regime is overthrown. Bondholders may therefore require a premium to compensate for the higher default risk due to the potentially odious character of these debts. On the basis of an original database of Cuban bonds, the paper shows the existence of a risk premium of at least 200 basis points which penalized bonds issued by the Spanish occupation regime. Bond market reactions to events changing the perception that the debts were unfair or that they would be repudiated are analysed on the basis of a structural VAR. © 2013 European Historical Economics Society.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Le Concept de Dettes Odieuses

info:eu-repo/semantics/publishe

Denouncing Odious Debts

Economists have suggested it was optimal to signal the odious character of bonds when they were issued. However, since the odious debt doctrine has not been recognized by any court, one could argue that denouncing odious debts is useless. Exploiting a unique historical episode, this paper quantifies the impact of protests on odious debts. In 1906, the Russian government floated a bond in Paris to cover the costs of its war against Japan but also to raise money to crush the political movements wishing to reform Russia’s political system. Issued without parliamentary consent, this loan met with fierce opposition. Press campaigns in Great Britain, France and Germany denounced its odious character. If failure or success is determined solely by the ability to prevent a loan from being issued, then the campaign failed. We argue, however, that failure or success should be determined in light of the financial costs imposed on the issuer for future loans and even the ability to force a postponement of these loans. We show that these campaigns increased the yields of all Russian bonds traded in Paris, and thus Russia’s future borrowing cost. Yields on the 1906 loan, which was specially targeted by the campaigns, rose even more. However, once the press campaigns stopped, yields experienced a declining trend, highlighting the important role the press may have on odious debts.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Place du sumatriptan spray dans la stratégie thérapeutique de la crise migraineuse

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Chemosensory pathways: from periphery to cortex

Chemosensory pathways: from periphery to cortex. The aim of this article is to summarise the anatomy of the chemosensory pathways. The vomeronasal organ, the olfactory system, the trigeminal system and the gustatory system will be reviewed in succession. For each of these systems, we will provide a description of the anatomy of the pathways sending the sensory message from the peripheral receptor to the cortical areas, passing through different relays in the nervous system. Particular emphasis will be paid to the anatomical features of the structures involved in chemosensory perception. This will help us to understand better how these systems interact and influence our social lives, our memories and our behaviour, and to evaluate patients with chemosensory dysfunction better

The early visual encoding of a face (N170) is viewpoint-dependent: a parametric ERP-adaptation study.

Visual representations of faces are extracted shortly after 100 ms in the human brain, leading to an occipito-temporal cortex N170 event-related potential (ERP). To understand the nature of this early visual representation, a full-front adapting face preceded a different or identical target face identity. The target face varied parametrically in head orientation from the adapting face (0-90°, 15° steps). The N170 elicited by the target face increased progressively from 0° up to 30° head orientation, with no further increase until 90°. The N170 decreased for repeated face identities, this effect being stable between 0° and 30° changes of viewpoint, and no effect beyond that angle. These observations suggest that a face is encoded in a view-dependent manner, being matched to either a full-front or a profile face view. Yet, individual face representations activated as early as the peak of the N170 generalize partially across view