Polyurethane Microparticles for Stimuli Response and Reduced Oxidative Degradation in Highly Porous Shape Memory Polymers.

Shape memory polymers (SMPs) have been found to be promising biomaterials for a variety of medical applications; however, the clinical translation of such technology is dependent on tailorable properties such as gravimetric changes in degradation environments. For SMPs synthesized from amino-alcohols, oxidation resulting in rapid mass loss may be problematic in terms of loss of material functionality as well as toxicity and cytocompatibility concerns. Control of gravimetric changes was achieved through the incorporation of small molecule antioxidants, either directly into the polymer matrix or included in microparticles to form a SMP composite material. With direct incorporation of small molecule phenolic antioxidant 2,2'-methylenebis(6- tert-butyl)-methylphenol (Methyl), SMPs displayed reduce strain recovery by more than 50% (Methyl) and increase elastic modulus from approximately 1.4 to 2.3 MPa, at the expense of the strain to failure being reduced from 45% to 32%. Importantly, such changes could not ensure retention of the antioxidants and therefore did not increase oxidative stability beyond 15 days in accelerated oxidative conditions (equivalent to approximately 800 days in porcine aneurysms) in all cases except for the inclusion of a hindered amine that capped network growth, which also resulted in shape memory reduction (only 80% recoverable strain achieved). However, the inclusion of antioxidants in microparticles was found to produce materials with similar thermomechanical ( Tg migration below 1.0 °C) and shape recovery of 100%, while increasing oxidative resistance compared to controls (oxidation onset was delayed by 3 days and material lifespan increased to approximately 20-22 days in accelerated oxidative solution or beyond 1000 days in the porcine aneurysm). The microparticle composite SMPs also act as a platform for environmental sensing, such as pH-dependent fluorescence shifts and payload release, as demonstrated by fluorescent dye studies using phloxine B and nile blue chloride and the release of antioxidants over a 3 week period. The use of polyurethane-urea microparticles in porous SMPs is demonstrated to increase biostability of the materials, by approximately 25%, and ultimately extend their lifespan for use in aneurysm occlusion as determined through calculated in vivo degradation rates corresponding to a porcine aneurysm environment.

Animal tuberculosis maintenance at low abundance of suitable wildlife reservoir hosts: A case study in northern Spain.

Animal tuberculosis (TB), which is caused by infection with members of the Mycobacterium tuberculosis complex (MTC), is a typical multi-host infection that flourishes at the livestock-wildlife interface. TB epidemiology is well characterized in the Mediterranean woodland habitats and Atlantic regions of southwestern Europe. However, much less is known about huge regions that do not form part of the two abovementioned settings, which have a low abundance of wild reservoirs. We hypothesized that MTC would be maintained in multi- rather than single-host communities in which wildlife would make a relatively low contribution to the maintenance of TB. Between 2011 and 2015, 7729 Eurasian wild boar (Sus scrofa) and 1729 wild ruminants were sampled for culture during hunting events on unfenced sites. In addition, 1058 wild ungulates were sampled on 23 fenced hunting estates. Infection prevalence data were modeled along with official data on cattle and goat TB, on livestock distribution and management, and on wild boar abundance. The mean individual MTC infection prevalence was 4.28% in wild boar, while the cattle skin test reactor percent was 0.17%. The prevalence of MTC infection in wild ungulates (mostly wild boar) from the fenced hunting estates was 11.6%. Modeling revealed that the main driver of TB in cattle was their management (beef; communal pastures). However, wild boar abundance, the prevalence of MTC infection in wild boar and the presence of fenced hunting estates also contributed to explaining cattle TB. The model used for goat TB identified communal pastures as a risk factor. The model for the prevalence of MTC infection in wild boar included wild boar abundance and communal pastures. We conclude that the MTC maintenance host community is most likely of a multi-host nature. While cattle and communal pastures pose the main risk regarding TB, it is also necessary to consider increasing wild boar densities and specific risks owing to fenced wildlife. We infer several management implications regarding wildlife management, the wildlife sampling strategy and laboratory testing, the peculiarities of fenced hunting estates, and the wildlife-livestock interface.

Chemical and enzymatic oxidation of alkylated benzo[a]pyrenes.

The chemical and enzymatic oxidations of 6-, 7- and 10-methylbenzo[a]-pyrenes, 6,10- and 7,10-dimethylbenzo[a]pyrenes and benzo[a]pyrene (BP) itself have been investigated to study the effects of alkyl substitution on the pathways of oxidation. The chemical oxidizing systems employed were Fenton's reagent (FeSO4/H2O2); trifluoroacetic acid-hydrogen peroxide (TFA/H2O2); thallium tristrifluoracetate in trifluoroacetic acid (TTFA/TFA) and H2SO4. The enzymatic systems were horseradish peroxidase (HRP/H2O2) and rat liver microsomes. The oxidations were investigated by electron paramagnetic resonance (EPR) spectroscopy to detect radical intermediates and by high performance liquid chromatography (HPLC) to separate the products. All the compounds studied produced radicals, identified as cationic species, in both H2SO4 and TTFA/TFA. In addition the 7-methyl-, 10-methyl- and 7,10-dimethyl-BP's produced 6-oxy radicals in some or all of the remaining oxidizing systems. Both chemically and enzymatically these same three compounds were observed to produce quinones as stable products. Microsomal oxidations gave the broadest range of products exhibiting HPLC peaks in the diol, quinone and phenol regions of the chromatograms, however, there were considerable differences between products from the individual derivatives and those from the parent molecule. 6-Methyl and 6,10-dimethyl-BP's showed no evidence of oxy radical intermediates or quinones under any set of conditions, the 6-substituent effectively blocking this oxidation pathway. The observations are consistent with the expected effects of alkyl substituents at particular positions and indicate that studies such as this one are potentially useful in better understanding oxidation and possible activation pathways of polycyclic aromatic hydrocarbons.

Screening of antioxidants and other compounds for antimutagenic properties towards benzo[a]pyrene-induced mutagenicity in strain TA98 of Salmonella typhimurium.

Antioxidants and several other compounds, some of which are known to inhibit carcinogenicity, have been screened for their effectiveness as inhibitors of benzo[a]pyrene (BP) mutagenicity towards Salmonella typhimurium strain TA98 in the Ames test. A total of 32 compounds were tested. In the assay, metabolic activation of BP (8.2 nmoles/plate) was mediated by the S9 fraction from beta-naphthoflavone-induced rat livers. Among compounds which are known to inhibit carcinogenicity, retinol, phenothiazine, disulfiram, phenethylisothiocyanate and phenylisothiocyanate were the most effective inhibitors of BP mutagenicity, being effective at equimolar concentrations. Several other compounds showed inhibition at higher concentrations of antioxidant and the remainder showed little or no inhibition. Dose-response curves have been obtained for the 17 most active compounds. No general pattern of inhibition is obvious from our studies, inhibitors are not drawn ;from any single class of compounds, nor does a particular compound necessarily appear to inhibit more than one mutagen.

The effect of substituted phenothiazines on the mutagenicity of benzo[a]pyrene.

The effect of phenothiazine and 11 of its derivatives on the mutagenicity of benzo[a]pyrene, as measured by the Ames test was investigated. Significant anti-mutagenic activity was detected for 10 phenothiazine derivatives, with the 2-chloro derivative being the most effective inhibitor tested and promazine the only phenothiazine drug tested which has no demonstrable inhibitory activity. It is considered that the anti-mutagenic activity and therefore potentially anticarcinogenic activity of these derivatives should be of interest to epidemiologists.