Il follow up del bambino con ipoacusia permanente

I programmi di identificazione precoce delle ipoacusie infantili permette di intraprendere rapidamente l’iter riabilitativo e protesico appropriato; nonostante ciò appare ancora elevato il numero di pazienti che non aderiscono al programma terapeutico. L’obiettivo di questo articolo è presentare i risultati di un’analisi strategica che prende in considerazione i punti di forza, i punti di debolezza, le opportunità e i rischi del processo di follow up audiologico/protesico/linguistico di bambini affetti da ipoacusia bilaterale permanente. Il follow up in questione, coinvolgendo bambini piccoli, implica il coinvolgimento di professionisti specializzati e inseriti in un team multidisciplinare e una gestione plurisettoriale complessa e prolungata. Nell’ambito del progetto finanziato dal Ministero della Salute Italiano CCM 2013 denominato “Programma regionale di identificazione, intervento e presa in carico precoci per la prevenzione dei disturbi comunicativi nei bambini con deficit uditivo” lo scopo di quest’analisi è stata quella di offrire delle raccomandazioni per armonizzare i criteri di valutazione dei risultati terapeutici e trarre spunto da questi per successivamente fornire delle linee guida riguardanti le metodiche più adeguate nella valutazione del bambino con ipoacusia permanente

Differentiation of normal and cancer cells induced by sulfhydryl reduction: biochemical and molecular mechanisms

We examined the morphological, biochemical and molecular outcome of a nonspecific sulfhydryl reduction in cells, obtained by supplementation of N-acetyl-L-cysteine (NAC) in a 0.1-10 mM concentration range. In human normal primary keratinocytes and in colon and ovary carcinoma cells we obtained evidences for: (i) a dose-dependent inhibition of proliferation without toxicity or apoptosis; (ii) a transition from a proliferative mesenchymal morphology to cell-specific differentiated structures; (iii) a noticeable increase in cell-cell and cell-substratum junctions; (iv) a relocation of the oncogenic beta-catenin at the cell-cell junctions; (v) inhibition of microtubules aggregation; (vi) upregulation of differentiation-related genes including p53, heat shock protein 27 gene, N-myc downstream-regulated gene 1, E-cadherin, and downregulation of cyclooxygenase-2; (vii) inhibition of c-Src tyrosine kinase. In conclusion, a thiol reduction devoid of toxicity as that operated by NAC apparently leads to terminal differentiation of normal and cancer cells through a pleiade of converging mechanisms, many of which are targets of the recently developed differentiation therapy

The HIV-1 Transactivator Factor (Tat) Induces Enterocyte Apoptosis through a Redox-Mediated Mechanism

The intestinal mucosa is an important target of human immunodeficiency virus (HIV) infection. HIV virus induces CD4+ T cell loss and epithelial damage which results in increased intestinal permeability. The mechanisms involved in nutrient malabsorption and alterations of intestinal mucosal architecture are unknown. We previously demonstrated that HIV-1 transactivator factor (Tat) induces an enterotoxic effect on intestinal epithelial cells that could be responsible for HIV-associated diarrhea. Since oxidative stress is implicated in the pathogenesis and morbidity of HIV infection, we evaluated whether Tat induces apoptosis of human enterocytes through oxidative stress, and whether the antioxidant N-acetylcysteine (NAC) could prevent it. Caco-2 and HT29 cells or human intestinal mucosa specimens were exposed to Tat alone or combined with NAC. In an in-vitro cell model, Tat increased the generation of reactive oxygen species and decreased antioxidant defenses as judged by a reduction in catalase activity and a reduced (GSH)/oxidized (GSSG) glutathione ratio. Tat also induced cytochrome c release from mitochondria to cytosol, and caspase-3 activation. Rectal dialysis samples from HIV-infected patients were positive for the oxidative stress marker 8-hydroxy-2′-deoxyguanosine. GSH/GSSG imbalance and apoptosis occurred in jejunal specimens from HIV-positive patients at baseline and from HIV-negative specimens exposed to Tat. Experiments with neutralizing anti-Tat antibodies showed that these effects were direct and specific. Pre-treatment with NAC prevented Tat-induced apoptosis and restored the glutathione balance in both the in-vitro and the ex-vivo model. These findings indicate that oxidative stress is one of the mechanism involved in HIV-intestinal disease

Global gene expression analysis in time series following N-acetyl L-cysteine induced epithelial differentiation of human normal and cancer cells in vitro

BACKGROUND: Cancer prevention trials using different types of antioxidant supplements have been carried out at several occasions and one of the investigated compounds has been the antioxidant N-acetyl-L-cysteine (NAC). Studies at the cellular level have previously demonstrated that a single supplementation of NAC induces a ten-fold more rapid differentiation in normal primary human keratinocytes as well as a reversion of a colon carcinoma cell line from neoplastic proliferation to apical-basolateral differentiation [1]. The investigated cells showed an early change in the organization of the cytoskeleton, several newly established adherens junctions with E-cadherin/β-catenin complexes and increased focal adhesions, all features characterizing the differentiation process. METHODS: In order to investigate the molecular mechanisms underlying the proliferation arrest and accelerated differentiation induced by NAC treatment of NHEK and Caco-2 cells in vitro, we performed global gene expression analysis of NAC treated cells in a time series (1, 12 and 24 hours post NAC treatment) using the Affymetrix GeneChip™ Human Genome U95Av2 chip, which contains approximately 12,000 previously characterized sequences. The treated samples were compared to the corresponding untreated culture at the same time point. RESULTS: Microarray data analysis revealed an increasing number of differentially expressed transcripts over time upon NAC treatment. The early response (1 hour) was transient, while a constitutive trend was commonly found among genes differentially regulated at later time points (12 and 24 hours). Connections to the induction of differentiation and inhibition of growth were identified for a majority of up- and down-regulated genes. All of the observed transcriptional changes, except for seven genes, were unique to either cell line. Only one gene, ID-1, was mutually regulated at 1 hour post treatment and might represent a common mediator of early NAC action. The detection of several genes that previously have been identified as stimulated or repressed during the differentiation of NHEK and Caco-2 provided validation of results. In addition, real-time kinetic PCR analysis of selected genes also verified the differential regulation as identified by the microarray platform. CONCLUSION: NAC induces a limited and transient early response followed by a more consistent and extensively different expression at later time points in both the normal and cancer cell lines investigated. The responses are largely related to inhibition of proliferation and stimulation of differentiation in both cell types but are almost completely lineage specific. ID-1 is indicated as an early mediator of NAC action

Neuroendocrine–immune disequilibrium and endometriosis: an interdisciplinary approach

Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity, affects one fourth of young women and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology and effective treatment strategies of endometriosis is still largely elusive. Inadequate immune and neuroendocrine responses are significantly involved in the pathophysiology of endometriosis, and key findings are summarized in the present review. We discuss here the role of different immune mechanisms particularly adhesion molecules, protein–glycan interactions, and pro-angiogenic mediators in the development and progression of the disease. Finally, we introduce the concept of endometrial dissemination as result of a neuroendocrine-immune disequilibrium in response to high levels of perceived stress caused by cardinal clinical symptoms of endometriosis

Valutazione dell’affidabilità strutturale della scala di sicurezza nel Polo Scientifico-Tecnologico dell’Università di Ferrara

In questa nota si propone uno studio dell’affidabilità strutturale della scala di sicurezza del corpo aule del Polo Scientifico – Tecnologico dell’Università di Ferrara. La struttura è composta da una reticolare metallica a via inferiore con una campata di 20 m di luce in semplice appoggio che si prolunga con uno sbalzo di 6.10 m. Allo sbalzo viene sospesa l’intera struttura della gabbia di scale. La passerella presenta forti vibrazioni trasversali sia in presenza di affollamento sia al passaggio di poche persone in corsa. Tale circostanza ha suggerito l’esecuzione di prove di carico statiche e prove dinamiche. Tali sperimentazioni hanno permesso di ottenere un modello numerico agli elementi finiti, in buon accordo con le evidenze sperimentali, da utilizzare come strumento di verifica della struttura sotto carichi statici e sismici. In particolare, le prove statiche hanno fatto uso di un sistema di contenitori riempiti d’acqua fino a realizzare un carico uniforme di 2.20 kPa esteso per una lunghezza di circa 13 metri. La misura degli spostamenti è stata eseguita tramite livello di precisione. Inoltre durante l’esecuzione della prova di carico è stata rilevata la temperatura di alcune aste della struttura. Le prove di carico dinamiche sono state effettuate tramite registrazioni accelerometriche delle oscillazione libere. Le caratteristiche modali della struttura sono state dedotte mediante metodi tradizionali di analisi modale sperimentale e confrontate con i risultati offerti da un modello numerico. Nonostante il disagio soggettivo percepito da alcune persone che percorrono la passerella, le verifiche svolte hanno escluso fenomeni di amplificazione delle azioni dinamiche indotte dalla folla