[Application of guidelines in clinical practice: a multicenter analysis of the treatment of membranous glomerulonephritis in Piedmont, Italy]. / Applicazione delle linee-guida nella realta' clinica: indagine multicentrica sul trattamento della glomerulonefrite membranosa in Piemonte.

The treatment of membranous glomerulonephritis (MGN) is controversial, especially in cases of no response to first-line treatment or multiple relapses. The Clinical Nephrology Group of Piedmont carried out a multicenter analysis of the treatment of patients affected by MGN in 15 nephrology units in Piedmont. The first treatment is usually started after a waiting period of 3-6 months in case of proteinuria in the nephrotic range but normal or slightly impaired renal function. A history of cancer, the presence of infectious disease, and secondary forms of MGN are criteria for exclusion from treatment. As first-line treatment, Piedmont nephrologists prescribe corticosteroids alternated with immunosuppressive drugs, generally preferring cyclophosphamide to chlorambucil. Only one nephrology unit uses cyclosporin A (CyA) as the first choice. In case of no response to treatment, a second therapeutic approach is undertaken after 2-12 months. Second-line treatment consists of CyA if immunosuppressive drugs were given before, and corticosteroids/ immunosuppressive drugs if CyA was the first treatment. A further choice may be ACTH or rituximab. In case of multiple relapses the treatment options are the same but previous immunosuppressive treatment, patient age, and the duration of kidney disease with a greater probability of renal failure and progression towards sclerosis require careful attention. Concern has been expressed regarding the potentially severe side effects of ACTH including myopathy, cataract and diabetes. In conclusion, the applied therapeutic approaches in Piedmont reflect the difficulty reported in the literature in identifying simple recommendations. ACTH and rituximab are increasingly preferred for the treatment of MGN and there is a need for prospective studies to determine the best protocol for rituximab and the safety profile of ACTH.

Modeling of multiple valued gene regulatory networks.

In silico modeling of Gene Regulatory Networks has gained a lot of attention recently as it gives a very powerful tool to experimental biologists to gather the knowledge gained from different biological experiments and understand the dynamics of the overall system. One of the key dynamics that is often interesting is the steady states of the networks which biologically corresponds to the cellular states. In our previous paper, we gave an efficient method called GenYsis to compute these steady states in Boolean representation of Gene Regulatory Network. It has been observed that protein may be expressed at more then two level of expression. This may result in different cellular outcomes. To address this issue, we present here a multiple-level modeling methodology that allows us to be more accurate. In this paper we extend our software GenYsis to model gene regulatory networks where each node in the network may take multiple values.