Search

Objectives: Glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), two incretin hormones, are developed to treat type II diabetes mellitus (DM). However, their clinical application is hampered by a short half-life in vivo. Accordingly, we developed novel, long-acting nanoformulations of both peptides consisting of self-associated GLP-1 and GIP with biocompatible and biodegradable sterically stabilized phospholipid nanomicelles (SSM). Methods: SSM composed of poly(ethylene glycol-2000)-grafted distearoylphosphatidylethanolamine (size, 15 nm)were prepared as previously described in our laboratory. Human GLP-1 or GIP was added to nanomicelles dispersed in saline, incubated for 2 h at room temperature and analyzed by circular dichroism and fluorescence spectroscopy. Results and discussion: α-Helicity of GLP-1 and GIP increased significantly in the presence of SSM (33α7%&29±3% respectively; n=3; mean±SD) compared to that in saline (11±1%&12±2% respectively; n=3; p<0.05). This conformation protects the peptides from hydrolysis and inactivation and is optimal for ligand-receptor interactions. Self-association of GLP-1 and GIP with SSM was confirmed by a significant increase in fluorescence intensity compared to that of the peptides in saline (n=3; p<0.05). Conclusions: Human GLP-1 and GIP interact avidly with SSM leading to increased α-helicity of the peptides. We propose that human GLP-1α and GIPα should be tested as novel, long-acting nanomedicines for type II DM. [ABSTRACT FROM AUTHOR]

Background: We aimed to analyse the outcome of universal newborn hearing screening (UNHS) and high‐risk hearing screening in neonatal intensive care unit (NICU) graduates in a tertiary care unit. Methods: The hearing screen programme comprises a 2‐stage automated auditory brainstem response protocol followed by a high‐risk hearing screen at 3–6 months. This study is a retrospective study of NICU graduates born between April 2002 and December 2009. Data on hearing screening, audiological assessment, and management were extracted from a computerized data management system (HITRACK). Results: Of 100,225 newborn infants, 2.9% were admitted to the NICU during the study period. The overall incidence of hearing loss (HL) of any type/severity was 35/1,000 infants. Of infants with HL, 92.4% had their first automated auditory brainstem response at/before 1 month of corrected age. The incidence of congenital permanent HL identified by the UNHS was 15.4/1,000. The corrected median age of diagnosis was 4.5 months (1–23.5 months). Of 2,552 NICU graduates who passed the UNHS, 75.5% were retested at 3–6 months of life. Twelve infants with permanent late‐onset HL were identified, raising the overall incidence of permanent HL to 19.9/1,000; 1.1/1,000 had auditory neuropathy. Of the 92 infants with HL, 89 (96.7%) had multiple risk factors. Conclusions: There is a high incidence of HL in NICU graduates; 22.6% were late in onset. An early rescreen in those who pass the UNHS is a beneficial step for this high risk population. [ABSTRACT FROM AUTHOR]