53 research outputs found
The diversity of abnormal hormone receptors in adrenal Cushing's syndrome allows novel pharmacological therapies
Proceedings of the Virtual 3rd UK Implementation Science Research Conference : Virtual conference. 16 and 17 July 2020.
Regulatory and 'economic' solvency standards for internationally active banks
Available from British Library Document Supply Centre-DSC:9350.8308(no 161) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo
Expression of vasopressin receptors in ACTH-independent macronodular bilateral adrenal hyperplasia causing Cushing's syndrome: molecular, immunohistochemical and pharmacological correlates
International audienceCortisol secretion in ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing Cushing's syndrome can be controlled by illegitimate receptors. The aim of the present study was to characterize the molecular, immunohistochemical, and pharmacological profiles of vasopressin receptors in cells derived from three patients with AIMAH (H1-H3), in order to evaluate the role of ectopic vasopressin receptors in the physiopathology of hypercortisolism. Expression of mRNAs encoding the vasopressin receptor types (V(1a), V(1b), and V(2)) were analyzed by RT-PCR in adrenal tissues. The presence of V(1a) and V(2) receptors was studied by immunohistochemistry on adrenal sections. The pharmacological profiles of vasopressin receptors involved in the control of cortisol secretion were investigated using the V(1a) receptor antagonist SR49059 and the V(2) receptor agonist [deamino-Cys(1), Val(4), D-Arg(8)]-vasopressin on cultured cells. The V(1a) receptor protein was present and functional in H1 and H3 tissues, whereas the V(1b) receptor was not expressed in any of the tissues. RT-PCR experiments revealed that V(2) receptor mRNAs were detected in the three tissues. In contrast, immunohistochemical and cell incubation studies showed that the V(2) receptor was involved in the stimulatory effect of AVP on cortisol secretion in H1 and H2, but not in H3 cells. Taken together, these data show that expression of functional ectopic V(2) receptors and repression of eutopic V(1a) receptor can coexist in some hyperplastic corticosteroidogenic tissues. They also reveal that immunohistochemical and incubation studies are essential for the characterization of ectopic receptors actually involved in the control of cortisol secretion by AIMAHs
Expression of vasopressin receptors in ACTH-independent macronodular bilateral adrenal hyperplasia causing Cushing's syndrome: molecular, immunohistochemical and pharmacological correlates
Role of neurotransmitters and neuropeptides in the regulation of the adrenal cortex
International audienc
Speciation of organic fractions does matter for aerosol source apportionment. Part 3: Combining off-line and on-line measurements
International audiencehe present study proposes an advanced methodology to refine the source apportionment of organic aerosol (OA). This methodology is based on the combination of offline and online datasets in a single Positive Matrix Factorization (PMF) analysis using the multilinear engine (ME-2) algorithm and a customized time synchronization procedure. It has been applied to data from measurements conducted in the Paris region (France) during a PM pollution event in March 2015. Measurements included OA ACSM (Aerosol Chemical Speciation Monitor) mass spectra and specific primary and secondary organic molecular markers from PM10 filters on their original time resolution (30 min for ACSM and 4 h for PM10 filters). Comparison with the conventional PMF analysis of the ACSM OA dataset (PMF-ACSM) showed very good agreement for the discrimination between primary and secondary OA fractions with about 75% of the OA mass of secondary origin. Furthermore, the use of the combined datasets allowed the deconvolution of 3 primary OA (POA) factors and 7 secondary OA (SOA) factors. A clear identification of the source/origin of 54% of the total SOA mass could be achieved thanks to specific molecular markers. Specifically, 28% of that fraction was linked to combustion sources (biomass burning and traffic emissions). A clear identification of primary traffic OA was also obtained using the PMF-combined analysis while PMF-ACSM only gave a proxy for this OA source in the form of total hydrocarbon-like OA (HOA) mass concentrations. In addition, the primary biomass burning-related OA source was explained by two OA factors, BBOA and OPOA-like BBOA. This new approach has showed undeniable advantages over the conventional approaches by providing valuable insights into the processes involved in SOA formation and their sources. However, the origins of highly oxidized SOA could not be fully identified due to the lack of specific molecular markers for such aged SOA
Comparison of five methodologies to apportion organic aerosol sources during a PM pollution event
International audienceThis study presents a comparison of five methodologies to apportion primary (POA) and secondary organic aerosol (SOA) sources from measurements performed in the Paris region (France) during a highly processed PM pollution event. POA fractions, estimated from EC-tracer method and positive matrix factorization (PMF) analyses, conducted on measurements from PM10 filters, aerosol chemical speciation monitor (ACSM) and offline aerosol mass spectrometry (AMS), were all comparable (2.2–3.7 μg m−3 as primary organic carbon (POC)). Associated relative uncertainties (measurement + model) on POC estimations ranged from 8 to 50%. The best apportionment of primary traffic OA was achieved using key markers (EC and 1-nitropyrene) in the chemical speciation-based PMF showing more pronounced rush-hour peaks and greater correlation with NOx than other traffic related POC factors. All biomass burning-related factors were in good agreement, with a typical diel profile and a night-time increase linked to residential heating. If PMF applied to ACSM data showed good agreement with other PMF outputs corrected from dust-related factors (coarse PM), discrepancies were observed between individual POA factors (traffic, biomass burning) and directly comparable SOA factors and highly oxidized OA. Similar secondary organic carbon (SOC) concentrations (3.3 ± 0.1 μg m−3) were obtained from all approaches, except the SOA-tracer method (1.8 μg m−3). Associated uncertainties ranged from 14 to 52% with larger uncertainties obtained for PMF-chemical data, EC- and SOA-tracer methods. This latter significantly underestimated total SOA loadings, even including biomass burning SOA, due to missing SOA classes and precursors. None of the approaches was able to identify the formation mechanisms and/or precursors responsible for the highly oxidized SOA fraction associated with nitrate- and/or sulfate-rich aerosols (35% of OA). We recommend the use of a combination of different methodologies to apportion the POC/SOC concentrations/contributions to get the highest level of confidence in the estimates obtained
Use of Specific Primary and Secondary Organic Markers for PM Source Apportionment Based on Positive Matrix Factorization (PMF)
International audienc
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