Lysosphingolipid Quantitation in Plasma and Dried-Blood Spots Using Targeted High-Resolution Mass Spectrometry.

Background: Sphingolipidoses are rare inherited metabolic diseases belonging to lysosomal diseases. Early and accurate diagnosis is crucial for effective management and treatment. In this study, we aimed to develop a robust method to accelerate the diagnosis of these sphingolipidoses using dried blood spots and plasma.

Large-scale screening of lipase acid deficiency in at risk population.

Background: Lysosomal acid lipase deficiency (LALD, OMIM#278000) is a rare lysosomal disorder with an autosomal recessive inheritance. The main clinical manifestations are related to a progressive accumulation of cholesteryl esters, triglycerides or both within the lysosome in different organs such as the liver, spleen, and cardiovascular system. A wide range of clinical severity is associated with LALD including a severe very rare antenatal/neonatal/infantile phenotype named Wolman disease and a late-onset form named cholesteryl ester storage disease (CESD).

Aldolase A deficiency: Report of new cases and literature review.

Aldolase A (ALDOA), is the predominant isoform of aldolase in skeletal muscle and erythrocytes that catalyzes the reversibleconversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate. Autosomal recessive mutations in are extremely rare and cause hemolytic anemia and/or recurrent episodes of rhabdomyolysis, usually precipitated by fever. In this report we describe, clinical, laboratory and genetic data of two novel unrelated patients harboring mutations in the gene who presented with episodic rhabdomyolysis, we review all previously published cases and discuss the most valuable features for diagnosis of this rare disorder.

Early Prediction of Graft Outcomes After Kidney Transplantation From Donors After Circulatory Death: Biomarkers and Transplantation Characteristics.

Background: This study aimed to identify transplantation characteristics and biomarkers that predict outcomes for kidney transplant (KT) patients from donors after circulatory death (DCDs).

Methods: Consecutive patients receiving a KT from a DCD in our center between 2014 and 2016 were included; the reference population was recipients with a living donor KT. The urinary tubular injury biomarker-to-creatinine ratio and serum lactate dehydrogenase (LDH) were measured at post-transplant days 1 and 3.

Budget impact analysis of heparin-bonded polytetrafluoroethylene grafts (Propaten) against standard polytetrafluoroethylene grafts for below-the-knee bypass in patients with critical limb ischaemia in France.

Objectives: To evaluate the budget impact of progressive replacement of standard polytetrafluoroethylene (PTFE) grafts by heparin-bound PTFE (Propaten) for below-the-knee (BTK) bypass in patients with critical limb ischaemia (CLI).

Design: From a review of the scientific literature, we calculated a theoretical BTK primary patency for Propaten grafts. Using the French hospital expenditure database (PMSI), we retrospectively estimated a rehospitalisation rate for standard PTFE grafts.

A thermolabile aldolase A mutant causes fever-induced recurrent rhabdomyolysis without hemolytic anemia.

Aldolase A deficiency has been reported as a rare cause of hemolytic anemia occasionally associated with myopathy. We identified a deleterious homozygous mutation in the ALDOA gene in 3 siblings with episodic rhabdomyolysis without hemolytic anemia. Myoglobinuria was always triggered by febrile illnesses.

Cellular and molecular mechanisms activating the cell death processes by chalcones: Critical structural effects.

Chalcones are naturally occurring compounds with diverse pharmacological activities. Chalcones derive from the common structure: 1,3-diphenylpropenone. The present study aims to better understand the mechanistic pathways triggering chalcones anticancer effects and providing evidences that minor structural difference could lead to important difference in mechanistic effect.

Evaluation of LOCI technology-based thyroid blood tests on the Dimension Vista analyzer.

Objectives: To assess the performance of thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) determinations by luminescent oxygen channeling immunoassay (LOCI) technology on the Dimension Vista analyzer (Siemens Healthcare Diagnostics).

Design & Methods: We assessed 1) functional sensitivity for TSH (FSe-TSH), and intra- and inter-assay variations for TSH, FT4 and FT3 on Vista; 2) comparisons of serum and heparin-treated plasma on Vista; 3) comparisons of a) plasma TSH by Vista versus electrochemiluminescence (ECLIA) on Roche Modular analyzer, and b) plasma FT4 and FT3 by Vista versus Immunotech-Beckman radioimmunoassay (RIA); and 4) association of albumin and prealbumin levels with free thyroid hormone concentrations on Vista.

Results: 1) FSe-TSH concentration was below 0.

[Medical treatments of hyperactive child: about the new pharmaceutical forms of methylphenidate marketed in France].

Multimodal treatment of hyperactive child includes psychostimulant medication, methylphenidate (MPH) marketed in France in its short-acting form since about ten years. We report our clinical experience about the first fifty methylphenidate responders who received one of the two sustained-release forms available since summer 2004, tablets of oros-methyphenidate (Concerta LP) or microgranule-filled capsules (Ritaline LP).

[A very high level in a cardiac troponin I assay].

Cardiac troponin I (TnIc) is a very sensitive and also a specific marker of myocardial injuries. We report here, the clinical case of a patient with a particularly important and brutal increase of the troponin during a myocardial infarction. A 64-year-old man was admitted to hospital.

5-lipoxygenase expression and activity in aorta from streptozotocin-induced diabetic rats.

We previously reported an activation of the 5-lipoxygenase pathway in aorta from streptozotocin-induced diabetic rats. The aim of this study was to investigate whether this activation was associated with an increased expression of 5-lipoxygenase, an increased cysteinyl leukotriene (CysLT) production in response to arachidonic acid or calcium ionophore A23187 and/or a hypersensitivity of the aorta to CysLTs in streptozotocin-induced diabetic rats. In aorta from diabetic and control rats, reverse transcriptase-PCR and western blot analysis with a specific 5-lipoxygenase antibody provided evidence for the presence of 5-lipoxygenase in aorta.

Changing the conformation state of cytochrome b558 initiates NADPH oxidase activation: MRP8/MRP14 regulation.

Phagocyte NADPH oxidase generates O2. for defense mechanisms and cellular signaling. Myeloid-related proteins MRP8 and MRP14 of the S100 family are EF-hand calcium-binding proteins.

Psychiatric adjustment following meningococcal disease treated on a PICU.

Objective: To describe the psychiatric status of child survivors of meningococcal disease and their mothers.

Design And Setting: Home interviews with 3-12 month follow-up.PATIENTS.

Involvement of cysteinyl leukotrienes in angiotensin II-induced contraction in isolated aortas from transgenic (mRen-2)27 rats.

Objectives: We have previously reported that 5-lipoxygenase-derived products, and particularly the cysteinyl leukotrienes (CysLTs), were involved in angiotensin II (Ang II)-induced contractions in isolated aortas from spontaneously hypertensive rats.

Design: The aim of this study was to assess the role of CysLTs in the vascular response to Ang II in an Ang II-dependent model of hypertension, the (mRen-2)27 transgenic rats (TGs).

Methods: Intact aortic rings from TG and normotensive Sprague-Dawley rats (SDs) were suspended in organ chambers for isometric tension development in response to Ang II.

Protein delivery by Pseudomonas type III secretion system: Ex vivo complementation of p67(phox)-deficient chronic granulomatous disease.

Bacterial type III secretion system drives the translocation of virulence factors into the cystosol of host target cells. In phagocytes and in Epstein-Barr virus immortalized B lymphocytes, NADPH oxidase generates O(-2) through an electron transfer chain the activity of which depends on the assembly of three, p67(phox), p47(phox) and p40(phox) cytosolic activating factors with Rac 1/2 and a membrane redox component, cytochrome b(558). In p67(phox) deficient chronic granulomatous disease (CGD) patients, p67-phox is missing and NADPH oxidase activity is abolished.

P67-phox-mediated NADPH oxidase assembly: imaging of cytochrome b558 liposomes by atomic force microscopy.

NADPH oxidase activity depends on the assembly of the cytosolic activating factors, p67-phox, p47-phox, p40-phox, and Rac with cytochrome b(558). The transition from an inactive to an active oxidase complex induces the transfer of electrons from NADPH to oxygen through cytochrome b(558). The assembly of oxidase complex was studied in vitro after reconstitution in a heterologous cell-free assay by using true noncontact mode atomic force microscopy.

Complementation of NADPH oxidase in p67-phox-deficient CGD patients p67-phox/p40-phox interaction.

Chronic granulomatous disease (CGD) is due to a functional defect of the O2- generating NADPH oxidase of phagocytes. Epstein-Barr-virus-immortalized B lymphocytes express all the constituents of oxidase with activity 100 times less than that of neutrophils. As in neutrophils, oxidase activity of Epstein-Barr-virus-immortalized B lymphocytes was shown to be defective in the different forms of CGD; these cells were used as a model for the complementation studies of two p67-phox-deficient CGD patients.

P40phox associates with the neutrophil Triton X-100-insoluble cytoskeletal fraction and PMA-activated membrane skeleton: a comparative study with P67phox and P47phox.

NADPH oxidase is an O2*- -generating enzyme found in phagocytes such as neutrophils. It is composed of a membrane-bound cytochrome b, the cytosolic proteins p67phox, p47phox, p40phox, and the G-protein p21rac. The system is dormant in resting cells but acquires catalytic activity on exposure to appropriate stimuli.

Biochemical and immunochemical properties of B lymphocyte cytochrome b558.

Like neutrophils, Epstein-Barr virus (EBV)-immortalized B lymphocytes express all constituents of the NADPH oxidase complex necessary to generate superoxide anion O2-. The NADPH oxidase activity in EBV-B lymphocytes is only 5% of that measured in neutrophils upon PMA stimulation. Cytochrome b558 is the sole redox membrane component of NADPH oxidase; it is the protein core around which cytosolic factors assemble in order to mediate oxidase activity.