TRα Mutations in Human.

Resistance to thyroid hormone alpha is an emerging syndrome, with up to now a limited number of published cases. Some features are common to most of the patients, but there is still some work to provide a comprehensive description of the full spectrum of the syndrome. A survey of the strategy to screen for and characterize the mutations in TR α gene is given.

[Immunohistochemistry using clone VE1 is an economic, specific and sensitive method for detecting the presence of BRAFV600E mutations in melanoma]. / L'immunohistochimie (clone VE1) est une méthode économique, spécifique et sensible pour détecter la présence d'une mutation BRAFV600E dans le mélanome.

BACKGROUND: Determination of BRAF mutation status is mandatory in the management of patients with inoperable stage IIIC or stage IV melanoma. Currently, molecular biology (MB) has been validated for detecting the presence of BRAF mutations. OBJECTIVE: To compare the sensitivity, specificity and cost of immunohistochemistry (IHC) (clone VE1) versus BM methods (qPCR and Sanger sequencing). PATIENTS AND METHODS: All the samples for which BRAF mutation status was requested between March 2013 and February 2015 at the cellular and molecular analysis laboratory of the Angers Hospital were included retrospectively and consecutively. The IHC (clone VE1) and BM analyses were performed with the same formalin-fixed paraffin embedded tumour samples. The cost of these two methods was determined on the basis of the cost for the French Health Insurance. RESULTS: Two hundred and seven samples were subjected to a determination of BRAF mutational status in IHC and BM. Only one sample was discordant between these two methods (positive in IHC, negative in BM). The sensitivity and specificity of the IHC was 100% and 99.25% respectively. The ratio of the cost of IHC/BM testing was 1:2.1. CONCLUSION: IHC (clone VE1) is a specific, sensitive and economic method for determining BRAFV600E mutation status. Nevertheless, this method must be validated in order to be integrated into a decisional algorithm, alongside BM methods, to determine whether targeted BRAF-inhibitor therapy is indicated.

Fondaparinux upregulates thrombomodulin and the endothelial protein C receptor during early-stage reperfusion in a rat model of myocardial infarction.

INTRODUCTION: Fondaparinux (FDX) was demonstrated to be cardioprotective in a rat model of myocardial ischemia reperfusion. In this model, FDX reduced infarct size after 2h of reperfusion, involving the activation of the survivor activating factor enhancement (SAFE) pathway as early as 30min post-reperfusion. Our aim was to study if this cardioprotection could be explained by anti-inflammatory mechanisms and a protective effect on vessels. METHODS: Wistar male rats were subjected to 40minutes (min) of myocardial ischemia, followed by 30min or 2h of reperfusion. Rats were randomized into four groups: control 30min (n=7), FDX 30min (n=7), control 2h (n=7), and FDX 2h (n=7). The FDX groups received 10mg/kg injection of FDX 10min prior to initiating reperfusion. We studied: 1) mRNA expression of endothelial markers, such as thrombomodulin (TM), endothelial protein C receptor (EPCR), and tissue factor (TF) and 2) proteic expression of ICAM-1, NF-κB, IκB, and JNK. Leukocyte infiltration was assessed by histochemistry. We also evaluated TM and EPCR mRNA expression in a model of isolated rat mesenteric arteries incubated with FDX. RESULTS: FDX upregulated the expression of TM and EPCR mRNA in the models of myocardial infarction and isolated mesenteric arteries. No difference was observed between the treated and control groups regarding the expression of pro-inflammatory signaling proteins, adhesion molecules, and leukocyte infiltration after 2h of reperfusion. CONCLUSION: The cardioprotective effect of FDX at early-stage reperfusion could be related to vascular protection, yet not to an anti-inflammatory effect.