Poly (D,L-lactide-co-glycolide) nanoparticles: Uptake by epithelial cells and cytotoxicity

This research article published by eXPRESS Polymer Letters Vol.8, No.3 (2014)Nanoparticles as drug delivery systems offer benefits such as protection of the encapsulated drug against degradation, site-specific targeting and prolonged blood circulation times. The aim of this study was to investigate nanoparticle uptake into Caco-2 cell monolayers, their co-localization within the lysosomal compartment and their cytotoxicity in different cell lines. Rhodamine-6G labelled poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles were prepared by a double emulsion solvent evaporation freeze-drying method. Uptake and co-localisation of PLGA nanoparticles in lysosomes were visualized by confocal laser scanning microscopy. The cytotoxicity of the nanoparticles was evaluated on different mammalian cells lines by means of Trypan blue exclusion and the MTS assay. The PLGA nanoparticles accumulated in the intercellular spaces of Caco-2 cell monolayers, but were also taken up transcellularly into the Caco-2 cells and partially co-localized within the lysosomal compartment indicating involvement of endocytosis during uptake. PLGA nanoparticles did not show cytotoxic effects in all three cell lines. Intact PLGA nanoparticles are therefore capable of moving across epithelial cell membranes partly by means of endocytosis without causing cytotoxic effects

A Spectroscopic Study of a Large Sample of Wolf-Rayet Galaxies

We analyze long-slit spectral observations of 39 Wolf-Rayet (WR) galaxies with heavy element mass fraction ranging over 2 orders of magnitude, from Zsun/50 to 2Zsun. Nearly all galaxies in our sample show broad WR emission in the blue region of the spectrum (the blue bump) consisting of an unresolved blend of N III 4640, C III 4650, C IV 4658 and He II 4686 emission lines. Broad C IV 5808 emission (the red bump) is detected in 30 galaxies. Additionally, weaker WR emission lines are identified, most often the N III 4512 and Si III 4565 lines, which have very rarely or never been seen and discussed before in WR galaxies. These emission features are characteristic of WN7-WN8 and WN9-WN11 stars respectively. We derive the numbers of early WC (WCE) and late WN (WNL) stars from the luminosities of the red and blue bumps, and the number of O stars from the luminosity of the Hbeta emission line. Additionally, we propose a new technique for deriving the numbers of WNL stars from the N III 4512 and Si III 4565 emission lines. This technique is potentially more precise than the blue bump method because it does not suffer from contamination of WCE and early WN (WNE) stars and nebular gaseous emission. The N(WR)/N(O+WR) ratio decreases with decreasing metallicity, in agreement with predictions of evolutionary synthesis models. The N(WC)/N(WN) ratios and the equivalent widths of the blue bump EW(4650) and of the red bump EW(5808) derived from observations are also in satisfactory agreement with theoretical predictions.Comment: 49 pages, 9 figures, to appear in Astrophys.

X-ray Spectral Survey of WGACAT Quasars, II: Optical and Radio Properties of Quasars with Low Energy X-ray Cut-offs

We have selected quasars with X-ray colors suggestive of a low energy cut-off, from the ROSAT PSPC pointed archive. We examine the radio and optical properties of these 13 quasars. Five out of the seven quasars with good optical spectra show associated optical absorption lines, with two having high delta-v candidate systems. Two other cut-off quasars show reddening associated with the quasar. We conclude that absorption is highly likely to be the cause of the X-ray cut-offs, and that the absorbing material associated with the quasars, not intervening along the line-of-sight. The suggestion that Gigahertz Peaked Sources are associated with X-ray cut-offs remains unclear with this expanded sample.Comment: 17 pages, LaTeX, including 2 Tables and 1 figure. Ap.J. in pres

The severe presentation and poor outcomes of rheumatic heart disease in Namibia: Lessons from the REMEDY study

Background. This paper reports the baseline characteristics and outcomes of 266 Namibian patients in the Global Registry of Rheumatic Heart Disease. Objective. To describe clinical findings and outcomes in a cohort of children and adults with rheumatic heart disease in Namibia. Methods. Prospective study of all patients with rheumatic heart disease at Windhoek Central Hospital between January 2010 and November 2012. Results. A total of 266 patients were enrolled; median age was 22 years, 72.6% were <30 years old and 60.5% female. The majority (62.8%) had moderate-severe disease; 48.9% were in congestive cardiac failure. Secondary antibiotic prophylaxis was used by 34.2%. Warfarin was used by 75.3% (n=64/85) with clinical indications. Forty-seven (17.6%) had previous valve interventions, of whom 40 (15.0%) had mechanical valve replacements. Over a 2-year follow-up period 19.1% of patients died. Severe valve involvement at enrolment was independently associated with mortality (24.6% v. 5.1% in those without severe disease; hazard ratio 4.9; 95% confidence interval 1.50 - 15.98). Sixty-five (29.8%) of the 218 without previous intervention had valvular intervention after enrolment. Conclusions. In Namibia rheumatic heart disease affects young people who present with severe disease and have a high case fatality rate. Rates of secondary prevention were low. These findings have informed the National Programme for Prevention and Control of Rheumatic Heart Disease in Namibia

Projections of Type 1 and Type 2 Diabetes Burden in the U.S. Population Aged <20 Years Through 2050: Dynamic modeling of incidence, mortality, and population growth

To forecast the number of U.S. individuals aged <20 years with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) through 2050, accounting for changing demography and diabetes incidence

Ankle brachial index combined with Framingham risk score to predict cardiovascular events and mortality - A meta-analysis

CONTEXT: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. OBJECTIVE: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. DATA SOURCES: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. STUDY SELECTION: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. DATA EXTRACTION: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. RESULTS: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. CONCLUSION: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS

Clinical evolution of beta cell function in youth with diabetes: the SEARCH for Diabetes in Youth study

Few studies have explored the epidemiology of beta cell loss in youth with diabetes. This report describes the evolution and major determinants of beta cell function, assessed by fasting C-peptide (FCP), in the SEARCH for Diabetes in Youth study

Admixture in the Hispanics of the San Luis Valley, Colorado, and its implications for complex trait gene mapping

Hispanic populations are a valuable resource that can and should facilitate the identification of complex trait genes by means of admixture mapping (AM). In this paper we focus on a particular Hispanic population living in the San Luis Valley (SLV) in Southern Colorado.We used a set of 22 Ancestry Informative Markers (AIMs) to describe the admixture process and dynamics in this population. AIMs are defined as genetic markers that exhibit allele frequency differences between parental populations ≥30%, and are more informative for studying admixed populations than random markers. The ancestral proportions of the SLV Hispanic population are estimated as 62.7 ± 2.1% European, 34.1 ± 1.9% Native American and 3.2 ± 1.5% West African. We also estimated the ancestral proportions of individuals using these AIMs. Population structure was demonstrated by the excess association of unlinked markers, the correlation between estimates of admixture based on unlinked marker sets, and by a highly significant correlation between individual Native American ancestry and skin pigmentation (R 2 = 0.082, p < 0.001). We discuss the implications of these findings in disease gene mapping efforts.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65937/1/j.1529-8817.2003.00084.x.pd