Synthetic Geopolymers for Controlled Delivery of Oxycodone: Adjustable and Nanostructured Porosity Enables Tunable and Sustained Drug Release

In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2∶1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial

Breakdown of phylogenetic signal: a survey of microsatellite densities in 454 shotgun sequences from 154 non model Eukaryote species

Microsatellites are ubiquitous in Eukaryotic genomes. A more complete understanding of their origin and spread can be gained from a comparison of their distribution within a phylogenetic context. Although information for model species is accumulating rapidly, it is insufficient due to a lack of species depth, thus intragroup variation is necessarily ignored. As such, apparent differences between groups may be overinflated and generalizations cannot be inferred until an analysis of the variation that exists within groups has been conducted. In this study, we examined microsatellite coverage and motif patterns from 454 shotgun sequences of 154 Eukaryote species from eight distantly related phyla (Cnidaria, Arthropoda, Onychophora, Bryozoa, Mollusca, Echinodermata, Chordata and Streptophyta) to test if a consistent phylogenetic pattern emerges from the microsatellite composition of these species. It is clear from our results that data from model species provide incomplete information regarding the existing microsatellite variability within the Eukaryotes. A very strong heterogeneity of microsatellite composition was found within most phyla, classes and even orders. Autocorrelation analyses indicated that while microsatellite contents of species within clades more recent than 200 Mya tend to be similar, the autocorrelation breaks down and becomes negative or non-significant with increasing divergence time. Therefore, the age of the taxon seems to be a primary factor in degrading the phylogenetic pattern present among related groups. The most recent classes or orders of Chordates still retain the pattern of their common ancestor. However, within older groups, such as classes of Arthropods, the phylogenetic pattern has been scrambled by the long independent evolution of the lineages.Emese Meglécz, Gabriel Nève, Ed Biffin and Michael G. Gardne

Polar vortex evolution during the 2002 Antarctic major warming as observed by the Odin satellite

In September 2002 the Antarctic polar vortex split in two under the influence of a sudden warming. During this event, the Odin satellite was able to measure both ozone (O3) and chlorine monoxide (ClO), a key constituent responsible for the so-called “ozone hole”, together with nitrous oxide (N2O), a dynamical tracer, and nitric acid (HNO3) and nitrogen dioxide (NO2), tracers of denitrification. The submillimeter radiometer (SMR) microwave instrument and the Optical Spectrograph and Infrared Imager System (OSIRIS) UV-visible light spectrometer (VIS) and IR instrument on board Odin have sounded the polar vortex during three different periods: before (19–20 September), during (24–25 September), and after (1–2 and 4–5 October) the vortex split. Odin observations coupled with the Reactive Processes Ruling the Ozone Budget in the Stratosphere (REPROBUS) chemical transport model at and above 500 K isentropic surfaces (heights above 18 km) reveal that on 19–20 September the Antarctic vortex was dynamically stable and chemically nominal: denitrified, with a nearly complete chlorine activation, and a 70% O3 loss at 500 K. On 25–26 September the unusual morphology of the vortex is monitored by the N2O observations. The measured ClO decay is consistent with other observations performed in 2002 and in the past. The vortex split episode is followed by a nearly complete deactivation of the ClO radicals on 1–2 October, leading to the end of the chemical O3 loss, while HNO3 and NO2 fields start increasing. This acceleration of the chlorine deactivation results from the warming of the Antarctic vortex in 2002, putting an early end to the polar stratospheric cloud season. The model simulation suggests that the vortex elongation toward regions of strong solar irradiance also favored the rapid reformation of ClONO2. The observed dynamical and chemical evolution of the 2002 polar vortex is qualitatively well reproduced by REPROBUS. Quantitative differences are mainly attributable to the too weak amounts of HNO3 in the model, which do not produce enough NO2 in presence of sunlight to deactivate chlorine as fast as observed by Odin

Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease

Genetic heterogeneity is a difficulty frequently encountered in the search for genes conferring susceptibility to prostate cancer. To circumvent this issue, we selected a large prostate cancer pedigree for genome-wide linkage analysis from a population that is genetically homogeneous. Selected cases and first-degree relatives were genotyped with Affymetrix 10K SNP arrays, identifying a 14 Mb haplotype on chromosome 5 (5p13–q12) inherited identical-by-descent (IBD) by multiple cases. Microsatellite genotyping of additional deceased case samples confirmed that a total of eight cases inherited the common haplotype (P=0.0017). Re-sequencing of eight prioritised candidate genes in the region in six selected individuals identified 15 SNPs segregating with the IBD haplotype, located within the ITGA2 gene. Three of these polymorphisms were selected for genotyping in an independent Tasmanian data set comprising 127 cases with familial prostate cancer, 412 sporadic cases and 319 unaffected controls. Two were associated with prostate cancer risk: rs3212649 (OR=1.67 (1.07–2.6), P=0.0009) and rs1126643 (OR=1.52 (1.01–2.28), P=0.0088). Significant association was observed in both familial and sporadic prostate cancer. Although the functional SNP remains to be identified, considerable circumstantial evidence, provided by in vivo and in vitro studies, supports a role for ITGA2 in tumour development

Formation and Properties of Gels Based on Lipo-plexes

Aqueous systems containing sodium taurodeoxycholate and, eventually, soybean lecithin were investigated. Depending on the relative amounts of two such species, molecular, micellar, vesicular, liquid crystalline, and solid phases were formed. In the presence of bovine serum albumin, micellar and vesicular systems form lipo-plexes. The latter self-organize into gels, depending on composition and thermal treatments. According to scanning electron microscopy, vesicle-based gels obtained from lipo-plexes form sponge-like entities, whereas micelle-based ones self-arrange in fibrous organizations. Gels are characterized by a significant viscoelasticity in a wide temperature and frequency range. Rheological data were interpreted by assuming strict relations between the system response and the self-organization of the lipo-plexes into gels. It was inferred that differences in the gel properties depend on the different self-assembly modes of the aggregates formed by the mentioned lipo-plexes. Use of the above systems in biomedical applications, mostly in the preparation of matrices requiring the use of smart and biocompatible gels, is suggested. © 2014 American Chemical Society