Objectives This research project focused on the inhibitory effectiveness of a novel antimicrobial gel (AMG) towards a panel of common microbes involved in wound infections. Methods A novel antimicrobial topical gel consisting of vitamin E TPGS (tocopherol polyethylene glycol succinate), ascorbyl palmitate, zinc aspartate, lavender oil and deionized distilled water was developed in our laboratory. Various in vitro techniques were used to determine the effectiveness of AMG on prokaryotic and eukaryotic microbes. Results In vitro experiments show that while AMG had varying inhibitory effects on both prokaryotic and eukaryotic microbes, there was a predilection for AMG to inhibit planktonic growth and biofilm formation of Staphylococcus species, most notably Methicillin Resistant Staphylococcus aureus (MRSA). The inhibitory effect of the AMK on planktonic growth was immediate with a four-fold reduction in growth, compared to controls, within 4 to 6 hrs of induction. Within 24 hrs S. aureus growth was minimal and complete inhibition of growth was achieved within 48 hrs. In an in vitro biofilm model, the AMG inhibited Staphylococcus biofilm attachment by 67% (density), 82% (mass) and 95% (viability). On pre-formed established biofilms, the AMG was able to inhibit 47% (density), 47% (mass) and 44% (viability) Staphylococcus biofilms. Antibiotic comparison experiments demonstrated that the MIC (minimum inhibitory concentration) of Mupirocin was Conclusions AMG is nontoxic to humans and canines and demonstrates potential for use in wound infections as an alternative to commonly prescribed antibiotics without the unintended drug resistance seen with antibiotics. AMG is an effective treatment option, this far in vitro, for Staphylococcus infections that are particularly prone to biofilm growth.

La glycoprotéine P ou Pgp est une protéine de transport transmembranaire qui a pour rôle principal d'évacuer hors des cellules les xénobiotiques et les toxines. Elle agit comme une pompe à efflux et est surexprimée par certaines cellules cancéreuses. Ainsi, via ce mécanisme, les cellules tumorales peuvent devenir résistantes aux antitumoraux et conduire à l'échec des traitements lors de la chimiothérapie anticancéreuse. Aussi, la modulation de l'activité de cette protéine peut être un des moyens permettant l'amélioration des traitements anticancéreux. La Pgp possède plusieurs sites de fixation de substrats dont deux sont relativement proches spatialement : un site à stéroïdes et un site à ATP permettant d'hydrolyser l'ATP, source d'énergie nécessaire au fonctionnement de la Pgp. Notre objectif a été de synthétiser des modulateurs bivalents stéroïdes/bras/nucléosides. Pour cela, nous avons dans un premier temps préparé des analogues de bases puriques et plus particulièrement des didéazapurines, les 5- et 6-azaindoles et les trioxopyrrolopyridines correspondant puis effectué la glycosylation de ces derniers. Dans un second temps, des modulateurs stéroïdiens ont été synthétisés : plusieurs ont montré une bonne activité modulatrice de la Pgp. Enfin, des bras polyéthylènes glycols de longueurs variables ont été reliés à l'adénine pour être ensuite fixés aux stéroïdes via une fonction amide / P-glycoprotein Pgp is a transmembrane transporter protein that protects cells from potentially toxic exogenous compounds. This protein acts as a molecular pump and is overexpressed in cancer cells. So via that mechanism, tumor cells exhibit intrinsic or acquired cross-resistance to diverse chemotherapeutic agents, resulting in the failure of chemotherapy for some cancers. The modulation of the efflux activity of that protein can be one of the mean that could increase anticancer treatments efficiency. Pgp has different substrates sites, two of which are spatially close : the steroid site and the ATP site, the latter is in charge of ATP hydrolysis which give the required energy for the Pgp efflux activity. Our goal was to synthesize bivalent modulators steroids/linker/nucleosides. First we have obtained purine bases analogues and particularly didéazapurines such as 5- and 6-azaindoles and the corresponding trioxopyrrolopyridines, then we have carried out the glycosylation of those compounds. Then, steroids modulators have been synthesized : some of them have shown a good modulation activity toward Pgp. Finally, polyethylene glycols chains with different length have been grafted on adenine so that they could be attached to the steroids via an amide function

Indiana University-Purdue University Indianapolis (IUPUI) / Reduction of the polymerization shrinkage stress inherent of dimethacrylate-based resin composites has been a work in progress since the phenomenon was first described by Dr. Rafael L. Bowen in 1967. Contemporary efforts to modify the composites or the curing protocols for polymerization have proven a challenging task with controversial results. Influenced by existing mathematical models relating exposure, curing time and depth of cure of resin composites, a novel method for the reduction of polymerization shrinkage stress is proposed. By polymerizing through a single aperture mask, a dental light curing unit is transformed from a planar light source to a point light source, and a fully cured, three-dimensional “bullet” shaped curing front is predicted for the cured resin below. So long as the edges of the bullet do not touch the cavity walls or floor, the shrinkage stress of the bullet is not transferred. Follow-up with an unmasked curing unit then fully polymerizes the restoration. By reducing the volume of uncured composite in contact with the cavity walls and floor, shrinkage stress of the restoration is also reduced. The objective of the present study was to demonstrate this curing phenomenon with a model resin composite using masks with aperture diameters of 0.5, 0.4, and 0.25 mm and curing times of 10, 20, 30, and 40 seconds. The resulting curing front was evaluated quantitatively and qualitatively. From this, mathematical models of the curing front were derived. Selected combinations of aperture mask and curing time were then investigated to evaluate the influence of this phenomenon on the degree of conversion, Knoop hardness, and polymerization shrinkage stress of the same model resin composite. Group differences were analyzed using a one-way ANOVA at 5% significance.

Indiana University-Purdue University Indianapolis (IUPUI) / Monomers like triethylene glycol dimethacrylate (TEGDMA) leach from dental composites and adhesives due to incomplete polymerization or polymer degradation. The release of these monomers causes a variety of reactions that can lead to cell death. This death can be either necrotic, which is characterized mainly by inflammation and injury to the surrounding tissues, or apoptotic, which elicits little inflammatory responses, if any at all. TEGDMA-induced apoptosis in human pulp has been reported recently. However, the molecular mechanisms and the apoptotic (pro and anti) proteins involved in this process remain unclear. The objective of this study was to determine the apoptotic proteins expressed or suppressed during TEGDMA-induced apoptosis. Human pulp fibroblasts (HPFs) were incubated for 24 hours with different TEGDMA concentrations (0.125-1.0 mM). Cytotoxicity was determined using the cytotoxicity Detection KitPLUS (Roche Applied Science, Mannheim, Germany). TEGDMA was shown to cause cell cytotoxicity at concentrations of 0.50 mM and up. The highest concentration with no significant cytotoxicity was used. Cells were incubated with or without 0.25 mM TEGDMA for 6 h and 24 h. Cell lysates were then prepared and the protein concentrations determined using the Bradford protein assay. A Human Apoptosis Array kit (Bio-Rad Hercules, CA ) was utilized to detect the relative levels of 43 apoptotic proteins. The results of this study showed statistically significant increases of multiple examined pro-apoptotic proteins. The anti-apoptotic proteins were also altered. Pro-apoptotic proteins involved in the intrinsic and extrinsic apoptotic pathways were increased significantly. The results indicated that TEGDMA has effects on both the extrinsic and intrinsic apoptotic pathways.

Yes / The peripheral nervous system has a limited innate capacity for self-repair following injury, and surgical intervention is often required. For injuries greater than a few millimeters autografting is standard practice although it is associated with donor site morbidity and is limited in its availability. Because of this, nerve guidance conduits (NGCs) can be viewed as an advantageous alternative, but currently have limited efficacy for short and large injury gaps in comparison to autograft. Current commercially available NGC designs rely on existing regulatory approved materials and traditional production methods, limiting improvement of their design. The aim of this study was to establish a novel method for NGC manufacture using a custom built laser-based microstereolithography (muSL) setup that incorporated a 405 nm laser source to produce 3D constructs with approximately 50 mum resolution from a photocurable poly(ethylene glycol) resin. These were evaluated by SEM, in vitro neuronal, Schwann and dorsal root ganglion culture and in vivo using a thy-1-YFP-H mouse common fibular nerve injury model. NGCs with dimensions of 1 mm internal diameter x 5 mm length with a wall thickness of 250 mum were fabricated and capable of supporting re-innervation across a 3 mm injury gap after 21 days, with results close to that of an autograft control. The study provides a technology platform for the rapid microfabrication of biocompatible materials, a novel method for in vivo evaluation, and a benchmark for future development in more advanced NGC designs, biodegradable and larger device sizes, and longer-term implantation studies.