Uptake and transport of novel amphiphilic polyelectrolyte-insulin nanocomplexes by caco-2 cells - towards oral insulin

“The original publication is available at www.springerlink.com”. Copyright SpringerPurpose: The influence of polymer architecture on cellular uptake and transport across Caco-2 cells of novel amphiphilic polyelectrolyte-insulin nanocomplexes was investigated. Method: Polyallylamine (PAA) (15 kDa) was grafted with palmitoyl chains (Pa) and subsequently modified with quaternary ammonium moieties (QPa). These two amphiphilic polyelectrolytes (APs) were tagged with rhodamine and their uptake by Caco-2 cells or their polyelectrolyte complexes (PECs) with fluorescein isothiocyanate-insulin (FITC-insulin) uptake were investigated using fluorescence microscopy. The integrity of the monolayer was determined by measurement of transepithelial electrical resistance (TEER). Insulin transport through Caco-2 monolayers was determined during TEER experiments. Result: Pa and insulin were co-localised in the cell membranes while QPa complexes were found within the cytoplasm. QPa complex uptake was not affected by calcium, cytochalasin D or nocodazole. Uptake was reduced by co-incubation with sodium azide, an active transport inhibitor. Both polymers opened tight junctions reversibly where the TEER values fell by up to 35 % within 30 minutes incubation with Caco-2 cells. Insulin transport through monolayers increased when QPa was used (0.27 ngmL-1 of insulin in basal compartment) compared to Pa (0.14 ngmL-1 of insulin in basal compartment) after 2 hours. Conclusion: These APs have been shown to be taken up by Caco-2 cells and reversibly open tight cell junctions. Further work is required to optimise these formulations with a view to maximising their potential to facilitate oral delivery of insulin.Peer reviewe

p Factor V Leiden but not the factor II 20210G>A mutation is a risk factor for premature coronary artery disease: a case-control study in Iran

Background: Factor V Leiden (FVL) and factor II c.*97G>A (rs1799963) are genetic risk factors for venous thromboembolism. Their contribution to coronary artery disease (CAD) is less clear. Objectives: This study aimed to investigate the association between FVL, rs1799963, and premature CAD in Iranians.Methods: We performed a genetic case-control study of 944 cases and 1081 controls from the premature CAD Milano-Iran study, including patients aged 18-55 (female) and 18-45 years (male) who underwent coronary angiography at the Tehran Heart Centre (Iran) in 2004-2011. Cases had luminal stenosis & GE;50% in at least 1 main coronary ar-tery or branch. Controls were age-and sex-matched with no CAD history. FVL and rs1799963 were genotyped using TaqMan SNP genotyping assays. Association was tested by logistic regression adjusted for matching factors and ethnicity. Effect modi-fication by sex and cardiovascular risk factors (metabolic [obesity, hypertension, hyperlipidemia, and diabetes], and smoking) was assessed.Results: The risk of premature CAD was increased by 50% in FVL carriers (adjusted odds ratio [adjOR] 1.54 [95% CI, 0.95-2.48]) and slightly reduced in rs1799963 carriers (adjOR 0.71 [95% CI, 0.40-1.27]). These effects were more pronounced in women than men (FVL, adjOR 1.66 vs 1.25; rs1799963, adjOR 0.60 vs 1.07). The risk of premature CAD was substantially increased in carriers of FVL with at least 1 metabolic risk factor compared with noncarriers without metabolic risk factors (adjOR 25.14 [95% CI, 12.51-50.52]).Conclusion: FVL but not FII rs1799963 was associated with an increased risk of CAD in young Iranians. This risk increased considerably when combined with metabolic car-diovascular risk factors.Clinical epidemiolog

Measuring of educational inequality in medical sciences sector from 2010 to 2016: A descriptive study in Iranian provinces

Background and Objectives: Access to equal educational opportunities is one of the fundamental rights in each country, and elimination of inequalities, especially in the higher education system, is one of the most important priorities. This study aimed to measure educational inequality in the medical sciences sector in Iranian provinces. Methods: In this study, educational inequality in medical sciences was measured using the Gini coefficient. The study indexes included the number of students, faculty members, staff, majors and educational budget. Data were analyzed using Stata 14 software. Results: During the study years, the Gini coefficient of the number of female students, male students, and faculty members showed a more or less decreasing trend from 0.51 to 0.46, from 0.53 to 0.46, and from 0.59 to 0.53, respectively. However, the values of inequality in the number of personnel working in educational sector and educational budget showed a slight increasing trend from 0.49 to 0.50 and from 0.53 to 0.54, respectively. According to the academic majors, the lowest Gini coefficient was related to non-continuous bachelor’s degree that varied from 0.13 to 0.17, and the highest value was related to fellowship degree ranging from 0.66 to 0.69 in the study years.     Conclusion: Despite reduced inequality in some educational indicators, there is a high inequality in the number of academic majors of some postgraduate degrees, number of students by gender, and educational budget, which requires policy makers to focus more on balanced distribution of educational infrastructures among provinces to provide equal educational opportunities