To understand the determinants of inhaled aerosol particle distribution and targeting in the lung, knowledge of regional deposition, lung morphology and regional ventilation, is crucial. No single ...imaging modality allows the acquisition of all such data together. Here we assessed the feasibility of dual-energy synchrotron radiation imaging to this end in anesthetized rabbits; both in normal lung (n = 6) and following methacholine (MCH)-induced bronchoconstriction (n = 6), a model of asthma. We used K-edge subtraction CT (KES) imaging to quantitatively map the regional deposition of iodine-containing aerosol particles. Morphological and regional ventilation images were obtained, followed by quantitative regional iodine deposition maps, after 5 and 10 minutes of aerosol administration. Iodine deposition was markedly inhomogeneous both in normal lung and after induced bronchoconstrition. Deposition was significantly reduced in the MCH group at both time points, with a strong dependency on inspiratory flow in both conditions (R
= 0.71; p < 0.0001). We demonstrate for the first time, the feasibility of KES CT for quantitative imaging of lung deposition of aerosol particles, regional ventilation and morphology. Since these are among the main factors determining lung aerosol deposition, we expect this imaging approach to bring new contributions to the understanding of lung aerosol delivery, targeting, and ultimately biological efficacy.
SLC5A8, proposed as a thyroid apical iodide transporter, was recently defined as a Na+-coupled transporter of short-chain fatty acid. To document the expression pattern of SLC5A8 in the thyroid, we ...analyzed the regulation of its expression in normal human thyrocytes in culture and in tissues with distinct functional activity. To determine whether SLC5A8 expression is altered in all thyroid carcinomas or only in particular subtypes, we investigated the level of its expression in a series of 50 hypofunctioning tumors. SLC5A8 expression was studied at the transcript level and compared with that of SLC26A4 or Pendrin and SLC5A5 or Na+/iodide symporter. SLC5A8 expression, unlike that of SLC5A5 and SLC26A4, was not regulated by TSH in normal human thyrocytes in culture and was not related to the functional state of thyroid tissue; toxic adenomas and adjacent resting tissues exhibited the same SLC5A8 transcript content. SLC5A8 expression was selectively down-regulated (40-fold) in papillary thyroid carcinomas of classical form (PTC-cf.). Methylation-specific PCR analyses showed that SLC5A8 was methylated in 90% of PTC-cf. and in about 20% of other papillary thyroid carcinomas. In a series of 52 PTC-cf., a low SLC5A8 expression was highly significantly associated with the presence of BRAF T1796A mutation. These data identify a relationship between the methylation-associated silencing of the tumor-suppressor gene SLC5A8 and the T1796A point mutation of the BRAF gene in the PTC-cf. subtype of thyroid carcinomas.
The uptake of iodide by epithelial thyroid cells requires the expression of a specific transporter, the Na
+/I
− symporter, NIS. Benign and malignant thyroid tumors of epithelial origin show a ...decrease up to a loss of iodide uptake activity. Previous studies of the human NIS (hNIS) gene expression in these tumors, based on the amplification of transcripts and/or immunohistochemical detection of the protein, have yielded divergent data; hNIS expression was found either increased or decreased. To get a new and integrated view of the alterations of hNIS expression in hypofunctioning thyroid tumors, we performed investigations of hNIS transcript and hNIS protein levels on the same tumors and paired normal tissue samples. HNIS, identified as a 75- to 80-kd species, was present in all normal tissue samples from euthyroid patients, but was undetectable, even at high membrane protein input, in all benign and malignant hypofunctioning thyroid tumors. By contrast, ∼50% of tumors contained hNIS transcripts. This dissociation between transcript and protein levels was not found for the transcript and protein encoded by the
PDS
gene assayed in the same tumors. The hNIS transcript-positive tumors contained small amounts of low-molecular mass hNIS-immunoreactive species identified as nonglycosylated hNIS. Tumors containing the nonmature form of hNIS exhibited a predominant intracellular immunolabeling. In conclusion, our data show that benign and malignant hypofunctioning thyroid tumors either no longer express hNIS protein or express only a very low amount of nonglycosylated hNIS and indicate that the impairment of
hNIS
gene expression might result from alterations at both transcriptional and posttranscriptional levels.
L’harmonisation du SMQ dans un LBM multi-sites est indispensable pour répondre aux exigences de la norme ISO 15189. Elle passe par une communication interne efficace et maîtrisée, difficile à mettre ...en place dans un laboratoire étendu à 15 sites techniques, éclatés sur 2 régions administratives, et regroupant plus de 200 personnes.
Pour pallier à ces difficultés, nous avons complété un réseau déjà établi de correspondants qualité, matériel et informatique dans chaque site par un groupe de 6 correspondants qualité multi-sites (CQM) compétents et volontaires, chacun chargé d’un sous-territoire régional.
Leur mission est de correspondre directement avec le personnel des sites dont ils ont la charge (techniciens, correspondants qualité et biologistes), de remonter les difficultés et interrogations rencontrées sur le terrain et de restituer au personnel les réponses et décisions prises lors de réunions avec le responsable qualité et le biologiste responsable du LBM. En 3ans, de nombreuses réunions, dont les comptes rendus sont diffusés à tout le personnel, ont ainsi permis de répondre précisément et uniformément à une multitude de questions très pratiques sur des sujets très divers.
Ce maillage territorial par les CQM a renforcé efficacement la communication interne, a facilité le déploiement harmonieux du SMQ au sein des sites, et s’est avéré très efficace en termes d’adhésion du personnel au respect des pratiques établies et d’implication dans la démarche qualité du laboratoire.
Cette harmonisation a été reconnue et considéré comme un point fort de la démarche par les évaluateurs du Cofrac et a largement contribué à l’accréditation du LBM multi-sites en 2014.
SUMMARY
1
There is an increasing demand in diagnostic radiology for extracting additional morphological and functional quantitative parameters from three‐dimensional computed tomography (CT) images. ...Synchrotron radiation computed tomography (SRCT) is the state‐of‐the‐art method in preclinical X‐ray CT, because its performance is close to the theoretical limits in terms of accuracy and precision.
2
The SRCT method with monochromatic X‐ray beams yields absolute high‐Z element contrast agent concentrations, without errors arising from beam hardening or scatter artefacts, by using digital subtraction techniques of the sinograms. Each pixel of the reconstructed difference images provides a quantitative concentration versus time curve of inhaled or injected high‐Z contrast agents (xenon or iodine) with a high sensitivity. This is the key point of two functional imaging techniques that were developed at the European Synchrotron Radiation Facility: brain perfusion and lung function (ventilation and perfusion).
3
These two imaging techniques provide parametric images expressed in absolute perfusion parameters (blood volume, blood flow, mean transit time and capillary permeability) or ventilation parameters (lung volume, regional lung ventilation, bronchial lumen size, regional airway and lung compliance) with a high accuracy and precision.
4
The aim of the present brief review is to give a snapshot of the status and perspectives of these two imaging techniques, with emphasis on the performances and interests for functional imaging. Two separate sections will then describe the results obtained so far using SRCT as an in vivo functional imaging tool for measuring changes in haemodynamics and ventilation, in the investigation of experimental pathophysiology and in the effects of therapeutic intervention.
Abstract Background and purpose Continuous positive airway pressure (CPAP) is an effective treatment for sleep apnea (SA), although the evidence for improving chronic heart failure (CHF) is ...inconclusive. Our aim was to evaluate the effect of CPAP treatment on the left ventricle ejection fraction (LVEF) among other cardiological variables in a randomized, multicenter, placebo (sham-CPAP)-controlled study. Methods After the selection procedure, 60 patients with CHF with LVEF < 45% and SA with an apnea–hypopnea index (AHI) > 10/h were evaluated at baseline, and after 3 months of treatment with optimal CPAP or sham-CPAP. The assessment was based on the LVEF, hypertension, daytime sleepiness (Epworth sleepiness scale ESS), quality of life (SF-36), New York Heart Scale (NYHA score), dyspnea (by using the Borg scale) and exercise tolerance (6-min walk test). Results The mean AHI was normalized in the optimal CPAP group but not in the sham-CPAP group. The LVEF showed a significant improvement in the group of patients treated with CPAP (2.5; 95% CI: 0.6 to 4.3), which was not observed in the sham-CPAP group (0.0; 95% CI: −2.1 to 2.1). However, the change in the LVEF from baseline to 3 months was not significantly greater in the whole group (obstructive and Cheyne–Stokes events) treated with CPAP than in the control group ( p : 0.07). In patients with only obstructive sleep apnea (OSA), who account for 83% of the total population, there was a significant improvement in the LVEF in the group of patients treated with CPAP but no such improvement in the sham-CPAP group. In this OSA group, the change in the LVEF from baseline to 3 months was significantly greater in the group treated with CPAP than in the sham-CPAP group ( p : 0.03). The other variables studied were not modified. When the patients were divided according to the severity of the LVEF (a LVEF cut-off of 30%), improvement was observed in those with a LVEF > 30. No changes were found in the other cardiological variables. Conclusions CPAP therapy proved to be useful in patients with associated sleep-disordered breathing and CHF. The improvement was more marked in patients with a LVEF > 30%. However, the increased LVEF in the CPAP group was not accompanied by changes in the other cardiological variables.
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