Budesonide è un principio attivo derivato dal cortisone. Come i cortisonici in genere, In caso di osteoporosi indotta da glucocorticoidi, i bifosfonati rappresentano farmaci di prima linea, mentre la vitamina D3 e la vitamina K2 sono considerati. I glucocorticoidi inalatori sono farmaci antiinfiammatori usati in associazione con polmonite durante il trattamento regolare a lungo termine con glucocorticoidi. Nonostante l’introduzione di farmaci biologici, i glucocorticoidi sono ancora utilizzati come trattamento standard nelle malattie infiammatorie croniche intestinali.

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Budesonide

Recentemente, piccole sequenze di microRNA si sono dimostrate importanti regolatori della trascrizione genica, e potrebbero avere un ruolo nella modulazione degli effetti gluclcorticoidi glucocorticoidi. Tali analisi, effettuate su prelievi dei pazienti ottenuti in tempi programmati durante il trattamento con glucocorticoidi, permetteranno inoltre di studiare i meccanismi molecolari coinvolti nel fenomeno di resistenza a questi farmaci.

To date, a curative pharmacological therapy for IBD does not exist and the therapeutic approach is mainly aimed at the treatment and control of the inflammation, through drugs capable of inducing and maintaining remission. In spite of the introduction in therapy of highly effective biological agents, glucocorticoids GCs are still employed to induce farmaic in moderate to severe IBD, but considerable inter-individual differences in their efficacy and side effects have been reported.

Given the high incidence of suboptimal response, associated with a significant number of side effects, that are particularly severe in paediatric patients, the identification of subjects that are most likely to gulcocorticoidi poorly to GCs is extremely important.

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Budesonide – Wikipedia

Genes involved in GC pharmacodynamic genes of the GC receptor heterocomplexand associated with the inflammatory pathway genes encoding for inflammatory mediators could be considered important candidates for an epigenetic approach involving microRNA miRNA. Emerging data have implicated the deregulated expression of certain miRNA networks in the pathogenesis of autoimmune and inflammatory diseases, such as IBD. The proposed research will develop new strategies for therapy personalization, based on clinical pharmacology assays, and in particular pharmacodynamic and pharmacogenomic assessments.

Side effects will be recorded at each clinical evaluation.

Moreover, preliminary experiments in our lab have revealed a relation between the GC clinical response of paediatric patients affected by chronic inflammatory diseases and the in vitro sensitivity of their leukocytes to these agents.

In vitro response to GCs will be evaluated by means of 3H thymidine incorporation assay performed on mononuclear cells isolated from peripheral blood. The expression of the selected candidate genes GC receptor heterocomplex genes carmaci genes associated with the inflammatory pathway will be evaluated in lymphocytes obtained at diagnosis, after 30 days and 12 months, using TaqMan gene expression assays.

The miRNA patients profiles at each time-points will be generated by farmacl an up-to-date real time based agnostic miRNA glucocorticoodi assay e.

This study will develop an innovative set of pharmacological tools, integrating pharmacodynamics and pharmacogenomics, to be applied at the optimization of GC therapy in paediatric IBD patients, in order to increase therapy efficacy and to reduce adverse events.

Quality of life is severely affected in IBD, due to the chronic character of the disease that implies frequent hospitalizations and aggressive therapies, with a significant risk of side effects and a considerable impact on health care costs.

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This project could provide new pharmacological markers useful to adjust treatment a priori, with glucoccorticoidi important impact on improved cure rates, avoiding inadequate regimens, and this is particularly important in paediatric patients, and reducing overall heath-care cost. Salta al contenuto principale. Marker predittivi della risposta al trattamento con glucocorticoidi in bambini con malattia infiammatoria cronica intestinale. Aims The proposed research will develop new strategies for therapy personalization, based on clinical pharmacology assays, and in particular pharmacodynamic and pharmacogenomic assessments.

Materials and methods In vitro response to GCs will be evaluated by means of 3H thymidine incorporation assay performed on mononuclear cells isolated from peripheral blood. Main Expected Results and Impact This study will develop an innovative set of pharmacological tools, integrating pharmacodynamics and pharmacogenomics, to be applied at the optimization of GC therapy in paediatric IBD patients, in order to increase therapy efficacy and to gucocorticoidi adverse events.

Significance and Relevance for National Health System SSN Quality of life is severely affected in IBD, due to the chronic character of the disease that implies frequent hospitalizations and aggressive therapies, with a significant risk of side effects and a considerable impact on health care costs.