Oral Insulin

Oral insulin is an exciting area of research and development in the field of diabetology. This brief review covers the various approaches used in the development of oral insulin, and highlights some of the recent data related to novel oral insulin preparation

Pericyte insulin receptors modulate retinal vascular remodeling and endothelial angiopoietin signaling

Pericytes regulate vascular development, stability and quiescence; their dysfunction contributes to diabetic retinopathy. To explore the role of insulin receptors in pericyte biology, we created pericyte insulin receptor knockout mice (PIRKO) by crossing PDGFR β-Cre mice with insulin receptor (Insr) floxed mice. Their neonatal retinal vasculature exhibited peri-venous hypervascularity with venular dilatation, plus increased angiogenic sprouting in superficial and deep layers. Pericyte coverage of capillaries was unaltered in peri-venous and peri-arterial plexi and no differences in vascular regression or endothelial proliferation were apparent. Isolated brain pericytes from PIRKO had decreased angiopoietin-1 mRNA, whereas retinal and lung angiopoietin-2 mRNA was increased. Endothelial phospho-Tie2 staining was diminished and FoxO1 was more frequently nuclear localized in the peri-venous plexus of PIRKO, in keeping with reduced angiopoietin-Tie2 signaling. Silencing of Insr in human brain pericytes led to reduced insulin-stimulated angiopoietin-1 secretion, and conditioned media from these cells was less able to induce Tie2 phosphorylation in human endothelial cells. Hence, insulin signaling in pericytes promotes angiopoietin-1 secretion and endothelial Tie2 signaling and perturbation of this leads to excessive vascular sprouting and venous plexus abnormalities. This phenotype mimics elements of diabetic retinopathy, and future work should evaluate pericyte insulin signaling in this disease

Flexural and diametral tensile strength of composite resins

This study evaluated the flexural strength (sf) and the diametral tensile strength (st) of light-cured composite resins, testing the hypothesis that there is a positive relation between these properties. Twenty specimens were fabricated for each material (Filtek Z250- 3M-Espe; AM- Amelogen, Ultradent; VE- Vit-l-escence, Ultradent; EX- Esthet-X, Dentsply/Caulk), following ISO 4049 and ANSI/ADA 27 specifications and the manufacturers’ instructions. For the st test, cylindrical shaped (4 mm x 6 mm) specimens (n = 10) were placed with their long axes perpendicular to the applied compressive load at a crosshead speed of 1.0 mm/min. The sf was measured using the 3-point bending test, in which bar shaped specimens (n = 10) were tested at a crosshead speed of 0.5 mm/min. Both tests were performed in a universal testing machine (EMIC 2000) recording the fracture load (N). Strength values (MPa) were calculated and statistically analyzed by ANOVA and Tukey (a = 0.05). The mean and standard deviation values (MPa) were Z250-45.06 ± 5.7; AM-35.61 ± 5.4; VE-34.45 ± 7.8; and EX-42.87 ± 6.6 for st; and Z250-126.52 ± 3.3; AM-87.75 ± 3.8; VE-104.66 ± 4.4; and EX-119.48 ± 2.1 for sf. EX and Z250 showed higher st and sf values than the other materials evaluated (p < 0.05), which followed a decreasing trend of mean values. The results confirmed the study hypothesis, showing a positive relation between the material properties examined

Application of bile acids in drug formulation and delivery

Bile acids are naturally produced in humans and are known to provide human health benefits through their endocrinological, microfloral, metabolic and other åffects that are still to be elucidated. In recent years, there has been a growing interest in using bile acids as absorption enhancers for drug delivery. Bile acids are amphiphilic molecules with a unique ability to facilitate and promote drug permeation through biological membranes. The role of bile acids in promoting drug permeation has been experimentally illustrated in various pharmaceutical formulations including oral, nasal, ocular, buccal, pulmonary and rectal delivery as well as through the blood–brain barrier. Recently, bile acids have drawn attention in the field of drug delivery due to their ability to act as a drug carrier system in the form of mixed micelles, bilosomes and chemical conjugates with drug molecules. Bile acids have demonstrated a unique ability to enhance the epithelial transport of hydrophilic drugs through the paracellular route and that of hydrophobic compounds through both paracellular and transcellular routes. The aim of this review is to discuss various chemical and pharmaceutical aspects of BAs and their potential applications in drug formulation and delivery