Déterminants de la fibrose interstitielle et de l'atrophie tubulaire évalués un an après la transplantation rénale

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF

CyDEPMPOs: A class of stable cyclic DEPMPO derivatives with improved properties as mechanistic markers of stereoselective hydroxyl radical adduct formation in biological systems

International audienceThe cis/trans diastereoisomeric composition of hydroxyl radical adducts to chiral cyclic nitrones can beused to approach mechanisms of free radical formation in biological systems. Such determination isgreatly simplified when both diastereoisomers have ESR spectra with at least two non-overlapping lines.To achieve this prerequisite, a series of DEPMPO-derived spin traps bearing one unsubstituted or alkylsubstituted2-oxo-1,3,2-dioxaphosphorinane ring were synthesized and their structures were confirmedby X-ray diffraction, 1H, 13C and 31P NMR. These CyDEPMPOs nitrones showed variable lipophilicities andLD50 values on murine fibroblasts compatible with a safe use in biological spin trapping. All CyDEPMPOsformed persistent spin adducts with a series of free radicals, including superoxide and hydroxyl (i.e.,CyDEPMPOs-OH) and the in vitro half-life times of these two latter were at least as extended as thoseof parent DEPMPO. Using four methods of CyDEPMPOs-OH formation, the cis-CyDEPMPOs-OH percentagewas found significantly varied with substitution on the P-containing ring and, more interestingly, withthe generating system

A Novel Anti-TRPV6 Antibody and Its Application in Cancer Diagnosis In Vitro

Though the first discovery of TRPV6 channel expression in various tissues took place in the early 2000s, reliable tools for its protein detection in various cells and tissues are still missing. Here we show the generation and validation of rabbit polyclonal anti-TRPV6 channel antibodies (rb79–82) against four epitopes of 15 amino acids. Among them, only one antibody, rb79, was capable of detecting the full-length glycosylated form of the TRPV6 channel at around 100 kDa. The generated antibody was shown to be suitable for all in vitro applications, such as immunoblotting, immunoprecipitation, immunocytochemistry, immunofluorescence, etc. One of the most important applications is immunohistochemistry using the paraffin-embedded sections from cancer resection specimens. Using prostate cancer resection specimens, we have confirmed the absence of the TRPV6 protein in both healthy and benign hyperplasia, as well as its expression and correlation to the prostate cancer grades. Thus, the generated rabbit polyclonal anti-TRPV6 channel antibody rb79 is suitable for all in vitro diagnostic applications and particularly for the diagnosis in clinics using paraffin-embedded sections from patients suffering from various diseases and disorders involving the TRPV6 channel

Probing Properties, Stability, and Performances of Hierarchical Mesoporous Materials with Nanoscale Interfaces

International audienceNanocrystals growth mechanism embedded into mesoporous thin films has been determined directly from grazing incidence X-ray diffraction data. We have shown, for the first time, that surface capillary forces control the growth mechanism of nanocrystals into these nanoarchitectures. Moreover, these data allow an estimation of the surface tension of the nanocrystals organized into a 3-D nanoarchitecture. The analysis of the variations in the strain field of these nanocrystals gives information on the evolution of the microstructure of these mesoporous films, that is, the contacts among nanocrystals. This work represents the first application of grazing incidence X-ray for understanding stability and performances of mesoporous thin films. This approach can be used to understand the structural stability of these nanoarchitectures at high temperature

Investigation of subcellular acidic compartments using alpha-aminophosphonate 31P nuclear magnetic resonance probes.

The 31P nuclear magnetic resonance (NMR) characteristics, toxicity, and cellular penetration of five linear or cyclic alpha-aminophosphonate highly sensitive pH probes were investigated in Dictyostelium discoideum cells and isolated rat hearts and were compared with three phosphonic acid derivatives. The line width broadening at pH approximately pK(a), which was satisfactorily modelized for all compounds, was significantly limited in biological milieu for the new markers, affording a four- to sixfold better accuracy in pH determination. Cellular uptake or washout of nontoxic concentrations (< 15 mM) of alpha-aminophosphonates occurred by rapid passive permeation, whereas standard probes required a much slower fluid-phase pinocytosis and transport processes that could ultimately lead to trapping. Using mild concentrations (< 4 mM) three alpha-aminophosphonates having 6 < pK(a) < 7 allowed an easy and simultaneous 31P NMR determination of cytosolic, acidic, and extracellular compartments in anoxic-reoxygenated or starving D. discoideum

New highly sensitive pH probes for 31P NMR spectroscopy. Spin-lattice relaxation time measurements as a function ofmolecular structure, temperature, pH, and biological medium.

International audienceNew uncharged a-aminophosphonates derived from diethyl(2-methylpyrrolidin-2-yl) phosphonate were synthesized by nucleophilic addition of dialkylphosphites on 2-methyl-1-pyrroline.These compounds were intended as enhanced 31P-NMR pH probes in biological systems. Compared to standard pH markers such asinorganic phosphate or methylphosphonate, they demonstrated in vitro low acidic pKa values (6.6 < pKa < 7.0), resonance peaksranging from 21 to 35 ppm, distinct from those of phosphorylated metabolites, and 3e4 times as sensitive (9.2 < Ddab < 9.9 ppm)as usual markers, such as inorganic phosphate or methylphosphonate. The detailed synthetic procedures for three representativenew pH probes, which were non-toxic (in the mM range) in rat isolated heart preparations, was reported. In a larger series of27 structurally related a-aminophosphonates, 1/T1 (31P) values were given in different conditions of milieu, temperature andpH. The data support unique features for these compounds to reveal acidic cellular compartments

Quantifying the contribution of the Megha-Tropiques mission to the estimation of daily accumulated rainfall in the Tropics

International audienceThis article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record

Involvement of CCL18 in allergic asthma.

Allergic asthma is associated with a pulmonary recruitment of Th type 2 cells, basophils, and eosinophils, mainly linked to chemokine production. CCL18 is a chemokine preferentially expressed in the lung, secreted by APCs, induced by Th2-type cytokines, and only present in humans. Therefore, CCL18 may be involved in allergic asthma. PBMC from asthmatics allergic to house dust mite cultured in the presence of Dermatophagoides pteronyssinus 1 (Der p 1) allergen secreted CCL18, 48 and 72 h after stimulation, whereas those from healthy donors did not. Part of CCL18 was directly derived from Der p 1-stimulated plasmacytoid dendritic cells, whereas the other part was linked to monocyte activation by IL-4 and IL-13 produced by Der p 1-stimulated T cells. In bronchoalveolar lavages from untreated asthmatic allergic patients, CCL18 was highly increased compared with controls. Functionally, CCL18 preferentially attracted in vitro-polarized Th2 cells and basophils, but not eosinophils and Th1 cells, and induced basophil histamine and intracellular calcium release. These data show a new function for CCL18, i.e. the recruitment of Th2 cells and basophils, and suggest that CCL18 may play a predominant role in allergic asthma.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe