Importance of lysosomal cysteine proteases in lung disease

The human lysosomal cysteine proteases are a family of 11 proteases whose members include cathepsins B, C, H, L, and S. The biology of these proteases was largely ignored for decades because of their lysosomal location and the belief that their function was limited to the terminal degradation of proteins. In the past 10 years, this view has changed as these proteases have been found to have specific functions within cells. This review highlights some of these functions, specifically their roles in matrix remodeling and in regulating the immune response, and their relationship to lung diseases

INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes

Background The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from individuals with newly diagnosed type 1 diabetes combined with centralised collection of clinical samples to determine rates of decline in beta-cell function and identify novel biomarkers, which could be used for future stratification of phase 2 clinical trials. Methods In this context, we have developed a Master Protocol, based on the “backbone” of the INNODIA natural history study, which we believe could improve the delivery of phase 2 studies exploring the use of single or combinations of Investigational Medicinal Products (IMPs), designed to prevent or reverse declines in beta-cell function in individuals with newly diagnosed type 1 diabetes. Although many IMPs have demonstrated potential efficacy in phase 2 studies, few subsequent phase 3 studies have confirmed these benefits. Currently, phase 2 drug development for this indication is limited by poor evaluation of drug dosage and lack of mechanistic data to understand variable responses to the IMPs. Identification of biomarkers which might permit more robust stratification of participants at baseline has been slow. Discussion The Master Protocol provides (1) standardised assessment of efficacy and safety, (2) comparable collection of mechanistic data, (3) the opportunity to include adaptive designs and the use of shared control groups in the evaluation of combination therapies, and (4) benefits of greater understanding of endpoint variation to ensure more robust sample size calculations and future baseline stratification using existing and novel biomarkers

De carmine Latino quod Pervigilium Veneris inscribitur.

"Dissertatio inauguralis philologica quam consensu et auctoritate amplissimi philosophorum ordinis in Universitate literaria Gryphica ad summos in philosophia honores rite adipiscendos die XVIII. Aprilis hora X."Includes bibliographical references.Mode of access: Internet

Continuous glucose monitoring in children, adolescents, and adults with type 1 diabetes mellitus: analysis from the prospective DPV diabetes documentation and quality management system from Germany and Austria

OBJECTIVE: To determine frequency, duration, and relationship of continuous glucose monitoring (CGM) to glycemic control and rate of hypoglycemia in children and adults in Germany and Austria. RESEARCH DESIGN AND METHODS: From 59,920 patients documented in the DPV (Diabetessoftware zur prospektiven Verlaufsdokumentation) database, 144,385 sensor days of 2874 patients using CGM between January 2008 and September 2010 were analyzed. RESULTS: Overall, 4.8% of patients used CGM. In pediatric patients, study period (p = 0.0309), age (p = 0.0140), insulin dose (p 30 d) had significantly lower HbA1c (p < 0.0016). Severe hypoglycemia was not reduced in patients using CGM for <30 d. CONCLUSIONS: CGM is still rarely used in Germany and Austria. CGM use is associated with a significant reduction of HbA1c in adults but not in children. Hypoglycemic events were not reduced, irrespective of age