Peripheral blood mononuclear cell response to YKL-40 and Galectin-3 in cystic fibrosis.

BACKGROUND: Elevated circulating levels of YKL-40 correlate with disease severity in Cystic Fibrosis (CF), but the role of YKL-40 in the inflammatory response in CF is still under investigation. Our main goal was to evaluate if YKL-40 can modulate the expression of major cytokines (IL-6, IL-10, IL-13) implicated in the inflammatory response in CF. A secondary goal was to explore the interactions between YKL-40 and other circulating proteins to determine the impacts on cytokine modulation. METHOD: Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of 83 adult CF patients in stable clinical condition. PBMCs were treated with human YKL-40 followed by the measure of IL-6, IL-10 and IL-13 gene expression. Protein arrays were used to explore the interactions between YKL-40 and circulating proteins. Interaction with Galectin-3 (GAL3) was identified, and confirmed by binding assay. Cytokine gene expressions were again monitored by RT-qPCR after PBMC treatment with GAL3, with or without YKL-40 co-stimulation. RESULTS: Following YKL-40 stimulation, PBMC gene expression of IL-6, IL-10 and IL-13 varies across patients. IL-6 and IL-13 are coexpressed, but this response was different in male and female patients. GAL3 protein was detected in the blood of CF patients, and a molecular interaction with YKL-40 was identified. GAL3 did not interfere with the YKL-40 stimulation of IL-6, IL-10 and IL-13 but may modulate the coexpression. CONCLUSION: We observed that YKL-40 stimulation had a variable impact on IL-6, IL-10, and IL-13 gene expression in CF PBMCs and uncovered an interaction between GAL3 and YKL-40 in the serum of CF patients. Our findings suggest that YKL-40 is not only a biomarker of disease severity in CF, but it might play an active role in the inflammatory pathophysiology of the disease.

[Toxic leucoencephalopathy after use of sniffed heroin, an unrecognized form of beneficial evolution]. / Leucoencéphalopathie toxique après consommation d'héroïne prisée "sniff", une forme méconnue d'évolution favorable.

INTRODUCTION: Serious leukoencephalopathy can be related to heroin injection or inhalation. OBSERVATION: We report the first case of leukoencephalopathy observed three weeks after a 46-year-old man sniffed heroin. The clinical presentation included cognitive and behaviour disorders, pyramidal irritation and slight gait instability. Blood and cerebrospinal fluid analyse were normal. Brain magnetic resonance imaging showed diffuse, symmetrical supratentorial white matter lesions producing high intense signals on FLAIR and b1000-weighted sequences. Proton spectroscopy revealed an increased rate of cholin, in favour of active demyelinated lesions. Brain biopsy showed intramyelinic oedema with reactive gliosis. After two and a half years, moderate attentional fluctuations and difficulties in initiating activities persisted. Repeated MRI showed a reduction of the leukoencephalopathy. CONCLUSION: Heroin could be a cause more common than thought of leukoencephalopathy. The clinical and radiological expression and prognosis could be related to the mode of consummation (inhalation, intravenous injection, sniffing). This parameter may modulate severity and localization of brain lesions. More systematic use of MRI for patients with psychiatric symptoms after heroin intoxications could lead to a better evaluation of heroin-related neurotoxicity and potentially improve prevention.

In vivo tissue characterization using magnetic techniques.

Among the few non-invasive methods to quantify liver iron deposits, magnetic resonance imaging (MRI) and biomagnetic liver susceptometry (BLS) have been considered the best to evaluate iron overload in the body. This diagnosis is necessary for patients who regularly receive red blood cells transfusion and that have a genetic disorder known as hemochromatosis. In this work, we present the evaluation of the clinical usefulness of MRI and BLS of hepatic tissue to quantify iron deposits in non-transfused and transfused patients. Liver iron evaluation by MRI and BLS were performed in a group of 48 patients. The MRI images weighted in T2 were acquired using multi-slice single-spin-echo (SSE) and single-slice multi-spin-echo (MSE), conducted on a 1.5 T whole body scanner. BLS measurements were performed using an ac superconducting susceptometer based on SQUID. Typically MRI is able to evaluate iron overload in liver as high as 30 mg/g(dry tissue) when using MRI scanners provided with specially designed pulse sequences. For higher iron concentrations susceptibility measurement works better than MRI to evaluate higher iron overloads in the liver, because in this case there is saturation of MRI signal.