Detection of monoclonal protein by capillary zone electrophoresis can be challenged by iodinated contrast agent interference: a case report

The detection of monoclonal immunoglobulins is a key element in the diagnosis of monoclonal gammopathy. In clinical practice, screening and measurement of monoclonal proteins are commonly performed using capillary zone electrophoresis (CZE). Some exogenous substances, such as iodinated contrast agents, absorb incident UV light at the same wavelengths as the peptide bonds and may therefore interfere with the detection of proteins in CZE. We herein use the description of a case to illustrate that iodinated contrast agents can mask the presence of monoclonal immunoglobulins in CZE and we discuss the strategy needed to confirm this interference. Performing immunofixation, immunosubtraction, or a second CZE at a distance from the first blood sample is not only necessary to confirm the presence of an iodinated contrast media interference but also to ensure the absence of monoclonal proteins

Signature Electromagnétique du Glucose dans le Sang Humain

National audienceCet article propose une caractérisation électromagnétique de solutions aqueuses contenant du glucose en concentrations variables. La nouveauté de notre travail réside dans des mesures large-bande, y compris à des fréquences relativement élevées. En outre, le comportement singulier sur une large bande de fréquence lié à la présence de glucose est ensuite observé de nouveau dans un milieu complexe : le sang humain

A case of IgE myeloma transformed into IgE-producing plasma cell leukaemia

This is a case report of a challenging diagnosis of IgE monoclonal gammopathy of undetermined significance, which transformed into myeloma, then transformed into IgE-producing plasma cell leukaemia in a 71-year-old male who was followed in Brest, France, from 2015 to 2019. The IgEproducing variant is the rarest sub-type of multiple myeloma, and plasma cell leukaemia is considered to be the rarest and the most aggressive of human monoclonal gammopathies. In November 2015, hypogammaglobulinemia was detected during a systematic check-up. A kappa light chain monoclonal gammopathy was first diagnosed due to an increase of the free kappa/lambda light chains ratio. No monoclonal immunoglobulin was detected by either serum protein electrophoresis (Capillarys 2, Sebia, Issy-les-Moulineaux, France) or immunofixation (Hydrasys 2, Sebia, Issy-les- Moulineaux, France). In June 2018, a blood smear led to the diagnosis of plasma cell leukaemia. A monoclonal peak was detected and identified as IgE-kappa. Analysis of an archival sample taken three years earlier, revealed the presence of a monoclonal IgE, which had been missed at diagnosis. Chemotherapy with bortezomib and dexamethasone was introduced. The patient survived 10 months after the diagnosis of leukaemia. This case shows that an abnormal free light chain ratio should be considered as a possible marker of IgE monoclonal gammopathy even in the absence of a solitary light chain revealed by immunofixation. In addition, the use of an undiluted serum may increase the sensitivity of the immunofixation for the detection of IgE monoclonal gammopathies compared to the 1:3 dilution recommended by the manufacturer

Thyroid hormone receptor isoforms are sequentially expressed in oligodendrocyte lineage cells during rat cerebral development

In the mammalian brain, thyroid hormones regulate myelination. Their actions are mediated by interactions with nuclear receptors that function as ligand-regulated transcription factors. Two genes, α and β, encode different isoforms, of which only the β and α1 isoforms are authentic nuclear triiodothyronine (T3)-receptors (NT3R). In agreement with the important role of T3 on myelination and oligodendrocyte generation, the presence of NT3Rs has been reported in oligodendrocytes and their precursors. We and others have shown that both progenitors and oligodendrocytes in vitro express the α1 and α2 isoforms, but the expression of the β1 isoform is confined to differentiated oligodendrocytes, suggesting that they have different functions. To establish if this is the case during development in vivo, we have studied NT3R isoform expression in glial cells isolated by density gradient centrifugation from rat brains of various ages. We report the presence of the α1 NT3R and its variant α2, but not that of the β1 isoform, in newborn rat glial progenitors. The pattern of expression of β1, both at the level of mRNA and protein, parallels the increase in the number of oligodendrocytes. We found a significant change in the kinetic parameters of [125I]-T3 binding to NT3Rs in these cells during the first month of life, consisting of an increase in the binding capacity that peaks with myelination, and a significative decrease in Kd that coincides with the switch from the α to the β1 isoform. Thus, the expression of NT3R isoforms in the rat oligodendrocyte lineage changes radically from the α to the β1 isoform during the period when oligodendrocytes differentiate from progenitors.INSERM/CSIC de coopération biomédicale franco-espagnole.Peer Reviewe

Usefulness of a regional probabilistic approach to determining design discharges of hydropower plants in Albania

This paper presents the results obtained using the PARDES-flood method in Albania to determine discharges of hydropower plants. The first part of the method is a regional probabilistic approach to extreme rainfall. The second part is related to the determination of extreme maximum peak discharges thanks to two probabilistic relations between statistical quantiles. The original approach in the first part lies in combining the probabilistic theory of Poisson’s process, regional analysis and the integration of particular phenomena linked to orographic features. The rivers studied in Albania include the Vjosa, which flows through the southern part of the country. It has a total length of 272 km, 80 km of which are in Greece. In this geographical area we have 13 rainfall stations at our disposal (not counting the numerous stations available nearby) and seven discharge measurement stations with data covering the period 1951-1992. The regional analysis of rainfall across this catchment area revealed a homogeneous precipitation regime. The rainfall-runoff probabilistic correlation analyses confirmed the relations from the PARDES model and revealed saturation at a return period of 4 years

Active and passive smoking - New insights on the molecular composition of different cigarette smoke aerosols by LDI-FTICRMS

International audienceThe aerosol generated when a cigarette is smoked is a significant indoor contaminant. Both smokers and non-smokers can be exposed to this class of pollutants. Nevertheless, they are not exposed to the same kind of smoke. The active smoker breathes in the mainstream smoke (MSS) during a puff, whereas the passive smoker inhales not only the smoke generated by the lit cigarette between two puffs (SSS) but also the smoke exhaled by active smokers (EXS). The aerosol fraction of EXS has until now been poorly documented; its composition is expected to be different from MSS. This study aims to investigate the complex composition of aerosol from EXS to better understand the difference in exposure between active and passive smokers. To address this, the in-situ laser desorption ionisation Fourier transform ion cyclotron mass spectrometry (LDI-FTICRMS) was used to characterise the aerosol composition of EXS from two different smokers. Results clearly indicated many similarities between EXS samples but also significant differences with MSS and SSS aerosol. The comparison of MSS and EXS aerosol allowed the chemicals retained by the active smoker's lungs to be identified, whereas the convolution of the EXS and SSS aerosol compositions were considered relevant to the exposition of a passive smoker. As a consequence, active smokers are thought to be mainly exposed to polar and poorly unsaturated oxygenated and nitrogenated organics, compared with poorly oxygenated but highly unsaturated compounds in passive smokers

Itch processing in the brain

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Immune Checkpoint Inhibitors in Melanoma: A Review of Pharmacokinetics and Exposure-Response Relationships

International audienceImmune checkpoint inhibitors are a new class of monoclonal antibodies that amplify T-cell-mediated immune responses against cancer cells. The introduction of these new drugs, first anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) and then anti-programmed death-1 (anti-PD1), was a major improvement in the treatment of advanced or metastatic melanoma, a highly immunogenic tumour. The development strategy for immune checkpoint immunotherapies differed from that traditionally used for cytotoxic therapies in oncology. The choices of doses at which to conduct clinical trials, and subsequently the choice of doses at which to use these new therapies, were not based on the identification of a maximum tolerated dose from dose-escalation studies; thus, pharmacokinetic and pharmacokinetic–pharmacodynamic modelling was essential. The studies conducted have shown that the pharmacokinetics of ipilimumab were linear and not time-dependent. In addition, there was a correlation between the trough concentrations of ipilimumab and its therapeutic efficacy. On the contrary, the anti-PD1 immunotherapies nivolumab and pembrolizumab had time-dependent pharmacokinetics. Their therapeutic efficacy was not related to their trough concentration, but there was a correlation between the clearance of anti-PD1 and the survival of melanoma patients. This review highlights the complexity of interpreting the exposure–response relationships of these agents. Further studies are needed to assess the value of therapeutic drug monitoring of immune checkpoint inhibitors in the treatment of melanoma

Capteur microonde à base de résonateur planaire pour une analyse glycémique in-situ

National audienceCet article présente les premiers résultats de la conception et du développement d’un capteur microonde basé sur un résonateur à stub quart d’onde. L’idée de ce travail est d’utiliser des tubes à essai standards tels que ceux utilisés au CHRU de Brest remplis d’une solution aqueuse de glucose pour en déterminer sa concentration. L’interaction entre le champ électromagnétique et la solution (eau/glucose) à mesurer peut être observée en mesurant les variations des paramètres S entre 2 et 8 GHz. La technique présentée ci-après peut être utilisée pour d’autres liquides et solutions aqueuses

A new method for determination of insoluble cell walls and soluble non starchy polysaccharides from plant materials

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