A Component of Retinal Light Adaptation Mediated by the Thyroid Hormone Cascade

Analysis with DNA-microrrays and real time PCR show that several genes involved in the thyroid hormone cascade, such as deiodinase 2 and 3 (Dio2 and Dio3) are differentially regulated by the circadian clock and by changes of the ambient light. The expression level of Dio2 in adult rats (2–3 months of age) kept continuously in darkness is modulated by the circadian clock and is up-regulated by 2 fold at midday. When the diurnal ambient light was on, the expression level of Dio2 increased by 4–8 fold and a consequent increase of the related protein was detected around the nuclei of retinal photoreceptors and of neurons in inner and outer nuclear layers. The expression level of Dio3 had a different temporal pattern and was down-regulated by diurnal light. Our results suggest that DIO2 and DIO3 have a role not only in the developing retina but also in the adult retina and are powerfully regulated by light. As the thyroid hormone is a ligand-inducible transcription factor controlling the expression of several target genes, the transcriptional activation of Dio2 could be a novel genomic component of light adaptation

Il Costo Degli Eventi Avversi Associati ad Afatinib, Erlotinib e Gefitinib Nel Trattamento del Tumore del Polmone non a Piccole Cellule con Mutazione EGFR

Costs of adverse events associated with afatinib, erlotinib, and gefitinib first-line therapies in advanced non-small-cell lung cancer harboring EGFR-activating mutationsIntroductionEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) afatinib, erlotinib, and gefitinib are an established treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutation.ObjectivesConsistent with published meta-analyses, this study compares the cost of management of the adverse events (AEs) associated with these three drugs from the perspective of the Italian National Health System (NHS).MethodsThe frequency of AEs was established based on a recently published meta-analysis. Only the costs of management of the AEs were considered. Resource utilization in the management of the AEs was estimated by a panel of Italian oncologists and based on previously published studies.ResultsThe mean cost per patient treated with afatinib, erlotinib, and gefitinib was €141.03, €90.74 and 121.87, respectively. With afatinib, the cost per patient and per AE of grades ≤2 and ≥3 was €36.70 and €104.33. With erlotinib, the cost per patient and per AE of grades ≤2 and ≥3 was €46.99 and €40.75, whereas the cost with gefitinib was €34.76 and €87.11, respectively.ConclusionIn advanced EGFR mutation-positive NSCLC patients, first-line treatment with erlotinib could reduce the cost of management of the AEs for the NHS

P23H opsin knock-in mice reveal a novel step in retinal rod disc morphogenesis

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