Search results for "PTC"

Valutazione dell’outcome a distanza post-PTCA: risultati del follow-up ad un anno

2002

Time-point and dosage of gene inactivation determine the tumor spectrum in conditional Ptch knockouts

2009

Mutations in Patched (PTCH) have been associated with tumors characteristic both for children [medulloblastoma (MB) and rhabdomyosarcoma (RMS)] and for elderly [basal cell carcinoma (BCC)]. The determinants of the variability in tumor onset and histology are unknown. We investigated the effects of the time-point and dosage of Ptch inactivation on tumor spectrum using conditional Ptch-knockout mice. Ptch heterozygosity induced prenatally resulted in the formation of RMS, which was accompanied by the silencing of the remaining wild-type Ptch allele. In contrast, RMS was observed neither after mono- nor biallelic postnatal deletion of Ptch. Postnatal biallelic deletion of Ptch led to BCC preca…

Nonsense codons suppression. An acute toxicity study of three optimized TRIDs in murine model, safety and tolerability evaluation.

2022

Stop mutations cause 11% of the genetic diseases, due to the introduction of a premature termination codon (PTC) in the mRNA, followed by the production of a truncated protein. A promising therapeutic approach is the suppression therapy by Translational Readthrough Inducing Drugs (TRIDs), restoring the expression of the protein. Recently, three new TRIDs (NV848, NV914, NV930) have been proposed, and validated by several in vitro assays, for the rescue of the CFTR protein, involved in Cystic Fibrosis disease. In this work, an acute toxicological study for the three TRIDs was conducted in vivo on mice, according to the OECD No.420 guidelines. Animals were divided into groups and treated with …

Alcune considerazioni e prospettive sul ruolo della pianificazione territoriale per la valuitazione strutturale e strategica in un processo partecipa…

2005

All'interno della procedura per la formazione del Piani territoriali di coordinamento provinciale viene proposta una metodologia per la valutazione e programmazione strutturale e strategica dei servizi d'area vasta in una visione policentrica all'interno di parchi. La procedura di valutazione della domanda e dell'offerta e quindi degli scenari di programmazione territoriale vengono strutturati in una copianificazione multilivello che coinvolge secondo i principi di sussidiarietà la programmazione regionale e le scelte localizzative a livello locale all'interno di ambiti intercomunali di ottimizzazione.

Economic, Social and Welfare Issues

2015

In late 2008 the three Baltic states were thrust into the heart of an intensely polarising international public debate on strategies to tackle the growing global economic crisis. The previous four years, following accession to the European Union (EU) in 2004, had witnessed rapid economic growth across the region, indeed the three recorded the highest GDP growth in the EU. Banks eased lending restrictions, foreign direct investment (FDI) inflows surged and Baltic businesses and consumers binged on cheap, readily available credit. Hubristic politicians increasingly talked of the inevitability of economic convergence with Western Europe. However, a gradual slowdown from late 2007 declined into…

La tecnica del rendez-vous nel trattamento palliativo degli itteri neoplastici: nostra esperienza

2004

Introduction: "Rendez-vous" technique (RV) assume contemporaneous percutaneous transhepatic choledochal drainage (PTCD) and endoscopic (ERCP) approach to make easier biliary cannulation when it fails for anatomic, neoplastic or iatrogenic causes, in subject unresectable at presentation ("not fit for surgery"). Matherials and methods: Over a 3 years period 618 ERCP were performed in the Service of Digestive Endoscopy in Section of General and Thoracic Surgery, 59 of whom (9%) failed for non-visualization of ampulla of Vater (25%), intradiverticular ampulla (54%) or anatomic defects (21%). Were attempted 44 pre-cut: 14 failed (close biliary stricture), and we proceed to RV. Results: 11/14 (79…

Franchisee Discontinuance and Failure Empirical Findings from Finland

2008

The present study focuses on franchisee discontinuances and failures during 1999–2001. The paper deals with notions relating to discontinuance and failure. Franchising is approached from entrepreneurs hip viewpoint and taken as a form of starting and conducting entrepreneurship and business. The study was carried out in 2002 in Finland. The 46 member franchisors of the Finnish Franchising Association (FFA) were surveyed. Altogether 33 responses were received, adding up to a response rate of 72%. The results were parallel with the findings of the previous international studies. The results indicate that the average annual franchisee turnover rate was 11% in 1999–2001 in the studied franchise…

PTC124 derivatives as a novel approach to improve the readthrough of premature stop codons in the CFTR gene.

2011

Background Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). Approximately 10% (worldwide) of patients have in-frame nonsense mutations (UAA, UAG or UGA class I mutations) in the CF trans-membrane regulator (CFTR) gene that result in premature stop codons (PTCs) in the messenger RNA (mRNA) generating truncated CFTR protein responsible for a severe CF phenotype. Pharmacological approaches have been proposed to directly overcome PTCs. Ataluren (PTC124) a small molecule that mimics the activity of aminoglycosides has been suggested to allow PTCs readthrough and to partially restore the protein function. However, des…

AZIONE READTHROUGH DI DERIVATI DEL PTC124 SU SISTEMI MODELLO CELLULARI E IN CELLULE DI EPITELIO BRONCHIALE-FC IB3.1 (CFTR F508/W1282X )

2013

Obiettivi specifici: Le mutazioni nonsenso (mutazioni STOP), un difetto genetico frequente negli individui affetti da Fibrosi Cistica (CF), causano la sintesi di proteine CFTR tronche e non funzionanti che sono associate ad un fenotipo più severo della CF (McKone EF. et al., Chest 2006). L’obiettivo del nostro studio è stato quello di disegnare derivati dell’Ataluren (PTC124), una ‘small molecule’ a cui è stata attribuita attività readthrough, e valutarne l’attività su tre differenti sistemi modello sperimentali contenenti codoni di STOP prematuri (UGA, UAG, UAA). Materiali e metodi: Sono state sintetizzate 24 molecole derivate dal PTC124 e analizzate mediante tecniche spettroscopiche per v…

Valutazione dell'azione readthorough della molecola PTC124 su sistemi modello cellulari contenenti mutazioni non senso e in cellule epiteliali bronch…

2013

Circa il 10% dei pazienti affetti da fibrosi cistica (FC) presenta nel gene CFTR mutazioni non senso (o 'stop': UGA, UAG or UAA, mutazioni di classe I) che bloccano prematuramente la sintesi della proteina. Attualmente non esiste una cura per questo tipo di mutazioni ma si sta cercando di individuare delle molecole che siano in grado di indurre la traduzione di codoni di stop prematuri (readthrough) che, rispetto a molecole già note come il G418, abbiano effetti collaterali ridotti ed una maggiore specificità per uno specifico codone. Una piccola molecola che sembra possedere una tale attività è il PTC124 (Welch, 2007). Ad oggi però non c’è ancora un consenso generale sul meccanismo di azio…