Binding of Pentagalloyl Glucose to Aortic Wall Proteins: Insights from Peptide Mapping and Simulated Docking Studies.

Pentagalloyl glucose (PGG) is currently being investigated as a non-surgical treatment for abdominal aortic aneurysms (AAAs); however, the molecular mechanisms of action of PGG on the AAA matrix components and the intra-luminal thrombus (ILT) still need to be better understood. To assess these interactions, we utilized peptide fingerprinting and molecular docking simulations to predict the binding of PGG to vascular proteins in normal and aneurysmal aorta, including matrix metalloproteinases (MMPs), cytokines, and fibrin. We performed PGG diffusion studies in pure fibrin gels and human ILT samples. PGG was predicted to bind with high affinity to most vascular proteins, the active sites of MMPs, and several cytokines known to be present in AAAs. Finally, despite potential binding to fibrin, PGG was shown to diffuse readily through thrombus at physiologic pressures. In conclusion, PGG can bind to all the normal and aneurysmal aorta protein components with high affinity, potentially protecting the tissue from degradation and exerting anti-inflammatory activities. Diffusion studies showed that thrombus presence in AAAs is not a barrier to endovascular treatment. Together, these results provide a deeper understanding of the clinical potential of PGG as a non-surgical treatment of AAAs.

Acidiferrimicrobium australe gen. nov., sp. nov., an acidophilic and obligately heterotrophic, member of the Actinobacteria that catalyses dissimilatory oxido-reduction of iron isolated from metal-rich acidic water in Chile.

A novel acidophilic member of the phylum Actinobacteria was isolated from an acidic, metal-contaminated stream draining from an abandoned underground coal mine (Trongol mine), situated close to Curanilahue, Biobío Region, Chile. The isolate (USS-CCA1T) was demonstrated to be a heterotroph that catalysed under aerobic conditions the oxidation of ferrous iron and the reduction of ferric iron under anaerobic conditions, but not the oxidation of sulfur nor hydrogen. USS-CCA1T is a Gram-positive, motile, short rod-shaped, mesophilic bacterium with a temperature growth optimum at 30 °C (range 20-39 °C). It was categorized as an extreme acidophile growing between 1.7 and 4.5 and optimally at pH 3.0. The G+C content of the chromosomal DNA of the isolate was 74.1 mol%, which is highly related to Aciditerrimonas ferrireducens IC-180T , (the most closely related genus; 94.4 % 16S rRNA gene identity), and higher than other acidophilic actinobacteria. The isolate (USS-CCA1T) was shown to form a distinct 16S rRNA clade from characterized acidophilic actinobacteria, well separated from the genera Acidimicrobium, Ferrimicrobium, Ferrithrix, 'Acidithrix' and Aciditerrimonas. Genomic indexes (ANIb, DDH, AAI, POCP) derived from the USS-CCA1T draft genome sequence (deposited at DDBJ/ENA/GenBank under the accession WJHE00000000) support assignment of the isolate to a new species and a new genus within the Acidimicrobiaceae family. Isolate USS-CCA1T is the designated type strain of the novel species Acidiferrimicrobium australe (=DSM 106828T,=RGM 2506T).

Production of radioactive particles for endovascular therapeutic interventions.

Recanalization is a common phenomenon that decreases the efficacy of embolization procedures. It can be inhibited by beta-radiation. Two novel ways of producing radioactive particles are described, by neutron beam irradiation of gold-containing microspheres, or by using the 32P binding capacity of zirconium-containing microspheres. Particles were tested in vivo, to assess their ability to deliver radioactivity locally, using canine renal artery, porcine rete mirabile, and rabbit ear embolization models. Both radioactive microspheres (198Au and 32P) showed no detectable activity outside the target territory. 32P microspheres demonstrated typical radiation changes in a porcine rete mirabile arteriovenous malformation model.