Chitosan-coated bovine serum albumin nanoparticles for topical tetrandrine delivery in glaucoma: in vitro and in vivo assessment.

Glaucoma is one of the leading causes of blindness. Therapies available suffer from several drawbacks including low bioavailability, repeated administration and poor patient compliance with adverse effects thereafter. In this study, bovine serum albumin nanoparticles (BSA-NPs) coated with chitosan(CS) were developed for the topical delivery of tetrandrine (TET) for glaucoma management. Optimized nanoparticles were prepared by desolvation. pH, BSA, CS and cross-linking agent concentrations effects on BSA-NPs colloidal properties were investigated. CS-BSA-NPs with particle size 237.9 nm and zeta potential 24 mV was selected for further evaluation. EE% exceeded 95% with sustained release profile. In vitro mucoadhesion was evaluated based on changes in viscosity and zeta potential upon incubation with mucin. Ex vivo transcorneal permeation was significantly enhanced for CS coated formulation. In vitro cell culture studies on corneal stromal fibroblasts revealed NPs biocompatibility with enhanced cellular uptake and improved antioxidant and anti-proliferative properties for the CS-coated formulation. Moreover, BSA-NPs were nonirritant as shown by HET-CAM test. Also, bioavailability in rabbit aqueous humor showed 2-fold increase for CS-TET-BSA-NPs compared to TET with a sustained reduction in intraocular pressure in a rabbit glaucoma model. Overall, results suggest CS-BSA-NPs as a promising platform for topical ocular TET delivery in the management of glaucoma.

Assessment of maturation status of tumor-infiltrating dendritic cells in invasive ductal carcinoma of the breast: relation with vascular endothelial growth factor expression.

OBJECTIVE: Poor immunogenicity has been described in breast carcinoma although dendritic cells, the major antigen presenters, are known to infiltrate the tumor. Vascular endothelial growth factor has been proposed to reduce local immune response in tumors. We investigated the maturation status of dendritic cells in invasive ductal carcinoma of the breast in relation to vascular endothelial growth factor expression and clinicopathological parameters. MATERIAL AND METHOD: Fifty invasive ductal carcinomas of the breast were immunostained with CD1a (marker of immature dendritic cells); CD83 (marker of mature dendritic cells), vascular endothelial growth factor, estrogen receptor and progesterone receptor. RESULTS: Mature dendritic cells were detected in 36 cases (72%), and correlated with smaller tumor size, negative lymph nodes, positive steroid receptor status, and lower grade (P < 0.001). Immature dendritic cells were found in 100% of cases and correlated only with negative steroid receptor expression (estrogen receptor and progesterone receptor) (P=0.006 and 0.020 respectively). Vascular endothelial growth factor expression was detected in 44 cases (88%), and correlated directly with positive nodal metastases (P=0.014), correlated inversely with mature dendritic cell count (P=0.005); and did not correlate with immature dendritic cell count (P=0.104). CONCLUSION: Mature dendritic cell count correlates with good prognostic features in invasive ductal carcinoma of the breast, suggesting their role in initiating primary anti-tumor immune response. Vascular endothelial growth factor expression may play a role in inhibition of dendritic cell maturation sequence in the tumor microenvironment.

Stent for Life Initiative placed at the forefront in Egypt 2011.

AIMS: Myocardial infarction is a medical emergency in which 25 to 35% of patients will die before receiving medical attention. The Stent for Life registry was launched to access the current situation of the Egyptian population presenting with STEMI, and to determine what were the barriers to providing patients with cardiac problems appropriate care. METHODS AND RESULTS: This registry was conducted at 14 centres covered all the Egyptian regions including 1,324 consecutive patients presenting with STEMI during the period between January 1st, 2011 to November, 2011. Fourteen centres and 38 interventionalists participated in this registry; only six centres are Pilot Centres (fulfilling the criteria for a primary PCI centre) and were assigned at the end of 2011. Cardiovascular risk factors were mainly smoking (60.5%), dyslipidaemia (46.0%), diabetes (51.4%) and hypertension (56.0%). The mean age at presentation was 56.01±10.61years and 75.0% were male. Only 5% of the STEMI patients arrived via the emergency medical system. Thrombus aspiration was done in 42.7% of patients in primary PCI group and 25.9% in rescue PCI group. Bare metal stents (BMS) were used in 80.7% of the stented patients while drug eluting stents (DES) were used in 19.3% of the stented patients. In-hospital mortality was 2.9% (1.4% in primary PCI group, 1.1% in patients treated with thrombolysis and 0.4% in patients receiving no reperfusion therapy). CONCLUSION: Despite the logistical difficulties, excellent outcomes for acute interventional reperfusion strategy in STEMI can be achieved in our country, possibly similar to those seen in the West. There is a strong need for making the practice of PCI in STEMI more widespread in developing regions.