DEVELOPMENT OF HIGH CAPACITY HYPERBRANCHED NITRIC OXIDE DONORS FOR CONTROLLING SUBCUTANEOUS INFLAMMATION

Implanted medical devices undergo complications the longer they remain in contact with tissue or blood. This rejection of foreign materials by our body is one of the largest reasons innovations in biomedical sensors and implanted technology are being held back. One means to hold off this unwanted response is through the utilization of nitric oxide (NO) releasing materials. Two unique NO releasing polymeric materials were synthesized and characterized before being implanted subcutaneously. Both NO releasing materials described used S-nitrosothiol (RSNO) chemistry as the main mechanism for NO release. The first material described covalently links an RSNO to the backbone of PVC while the second material has RSNOs covalently attached to a hyperbranched polyamidoamine (HPAMAM) molecule, which is then blended within a polymer matrix. A high reservoir of NO was observed in the NO releasing HPAMAM when compared to other NO releasing polymers. The two materials (SNAP-PVC, SNAP-HPAMAM blended in PVC) were implanted subcutaneously and were tested versus control polymers that did not release NO; materials were explanted after 1 and 15 days and histological characterization was completed. The inflammatory response was then observed through histological analysis and NO demonstrated anti-inflammatory properties, specifically by observing the presence of cells marked with CD11b, CD163, and iNOS. Fibrosis was also a major inflammatory response carefully observed. NO releasing implants showed a much more resolved state of inflammation and wound healing while the controls demonstrated signs of chronic inflammation and increased number of pro-inflammatory cells. The long lasting SNAP-HPAMAM PVC NO releasing materials showed a large reduction in chronic inflammatory macrophages marked with iNOS with a slight upregulation in anti-inflammatory macrophages after 15 days of implantation. Compared to control PVC implants, a significant reduction in fibrosis was observed as the encapsulation thickness was 120.28±36.1 µm while SNAP-PVC was 74.20±29.9 µm and SNAP-HPAMAM was 38.68±21.0 µm. A trend was seen in the reduction of CD11b+ cells with an increase in NO from the implants, along with an increasing trend of CD163+ cells. The presence of chronic inflammatory iNOS cells was also greatly reduced with the increase of NO to the surrounding subcutaneous tissue

SB103-12/13: Ad-Hoc Committee

SB103-12/13: Ad-Hoc Committee. This resolution passed during the May 8, 2013 meeting of the Associated Students of the University of Montana (ASUM)

S-Nitroso-N-Acetyl-D-Penicillamine modified hyperbranched polyamidoamine for high-capacity nitric oxide storage and release

Synthetic nitric oxide (NO)-donating materials have been shown to have many beneficial effects when incorporated into biomedical materials. When released in the correct dosage, NO has been shown to increase the biocompatibility of blood and tissue contacting materials, but materials are often limited in the amount of NO that can be administered over a period of time. To address this, hyperbranched polyamidoamine (HPAMAM) was modified with the S-nitrosothiol, S-nitroso-N-acetyl-D-penicillamine, and nitrosated to form a controlled, high-capacity NO-donating compound (SNAP-HPAMAM). This compound has the potential of modifying polymers to release NO over long periods of time by being blended into a variety of base polymers. Nitric oxide release was triggered by photoinitiation and through passive ion-mediated release seen under physiological conditions. A material that delivers the beneficial dose of NO over a long period of time would be able to greatly increase the biocompatibility of long-term implantable devices. Structural analysis of a generation 2 HPAMAM molecule was done through Fourier transform infrared spectroscopy (FTIR), 1H nuclear magnetic resonance spectroscopy (NMR), and matrix assisted laser desorption ionization, time of flight (MALDI-TOF) mass spectrometry. The NO capacity of the finalized generation 2 SNAP-HPAMAM compound was approximately 1.90 ± 0.116 µmol NO/mg. Quantification of the functional groups in the compound proved that an average of 6.40 ± 0.309 reactive primary amine sites were present compared to the 8 reactive sites on a perfectly synthesized generation 2 dendrimer. There is a substantial advantage of using the hyper-branched HPAMAM over purified dendrimers in terms of reduced labor and expense while still providing a high-capacity NO donor that can be blended into different polymer matrices

The Diagnosis, Clinical Course, Treatment, and Prevention of the Rabies Virus

Rabies, despite available vaccines, causes approximately 55,000 deaths every year. Diagnosing relies on noting physical behaviors such as hydrophobia, vomiting, fever, behavior changes, paralysis, and consciousness, as well as, using several methodologies to molecularly detect the presence of the virus. RABV often enters through a bite wound given that it is transmissible through saliva. Infection spreads from muscle fibers into the peripheral nervous system traveling to the central nervous system. Infection of the central nervous system can lead to encephalitis (furious rabies) or acute flaccid paralysis (paralytic rabies). Treatment relies heavily on the time of exposure. If the patient is diagnosed prior to being symptomatic, post-exposure prophylaxis (PEP) can be administered. However, once the patient has begun displaying symptoms, therapy success rates sharply decline. Prevention includes vaccinating during both pre- and post-exposures, as well as utilizing Stepwise Approach towards Rabies Elimination (SARE) to aid impoverished countries in declining their rabies mortality rates

Submillimeter Follow-up of WISE-Selected Hyperluminous Galaxies

We have used the Caltech Submillimeter Observatory (CSO) to follow-up a sample of WISE-selected, hyperluminous galaxies, so called W1W2-dropout galaxies. This is a rare (~ 1000 all-sky) population of galaxies at high redshift (peaks at z=2-3), that are faint or undetected by WISE at 3.4 and 4.6 um, yet are clearly detected at 12 and 22 um. The optical spectra of most of these galaxies show significant AGN activity. We observed 14 high-redshift (z > 1.7) W1W2-dropout galaxies with SHARC-II at 350 to 850 um, with 9 detections; and observed 18 with Bolocam at 1.1 mm, with five detections. Warm Spitzer follow-up of 25 targets at 3.6 and 4.5 um, as well as optical spectra of 12 targets are also presented in the paper. Combining WISE data with observations from warm Spitzer and CSO, we constructed their mid-IR to millimeter spectral energy distributions (SEDs). These SEDs have a consistent shape, showing significantly higher mid-IR to submm ratios than other galaxy templates, suggesting a hotter dust temperature. We estimate their dust temperatures to be 60-120 K using a single-temperature model. Their infrared luminosities are well over 10^{13} Lsun. These SEDs are not well fitted with existing galaxy templates, suggesting they are a new population with very high luminosity and hot dust. They are likely among the most luminous galaxies in the Universe. We argue that they are extreme cases of luminous, hot dust-obscured galaxies (DOGs), possibly representing a short evolutionary phase during galaxy merging and evolution. A better understanding of their long-wavelength properties needs ALMA as well as Herschel data.Comment: Will be Published on Sep 1, 2012 by Ap

Mining Public Domain Data to Develop Selective DYRK1A Inhibitors

Kinases represent one of the most intensively pursued groups of targets in modern-day drug discovery. Often it is desirable to achieve selective inhibition of the kinase of interest over the remaining ∼500 kinases in the human kinome. This is especially true when inhibitors are intended to be used to study the biology of the target of interest. We present a pipeline of open-source software that analyzes public domain data to repurpose compounds that have been used in previous kinase inhibitor development projects. We define the dual-specificity tyrosine-regulated kinase 1A (DYRK1A) as the kinase of interest, and by addition of a single methyl group to the chosen starting point we remove glycogen synthase kinase β (GSK3β) and cyclin-dependent kinase (CDK) inhibition. Thus, in an efficient manner we repurpose a GSK3β/CDK chemotype to deliver 8b, a highly selective DYRK1A inhibitor

Testing Lorentz Invariance with Neutrinos from Ultrahigh Energy Cosmic Ray Interactions

We have previously shown that a very small amount of Lorentz invariance violation (LIV), which suppresses photomeson interactions of ultrahigh energy cosmic rays (UHECRs) with cosmic background radiation (CBR) photons, can produce a spectrum of cosmic rays that is consistent with that currently observed by the Pierre Auger Observatory (PAO) and HiRes experiments. Here, we calculate the corresponding flux of high energy neutrinos generated by the propagation of UHECR protons through the CBR in the presence of LIV. We find that LIV produces a reduction in the flux of the highest energy neutrinos and a reduction in the energy of the peak of the neutrino energy flux spectrum, both depending on the strength of the LIV. Thus, observations of the UHE neutrino spectrum provide a clear test for the existence and amount of LIV at the highest energies. We further discuss the ability of current and future proposed detectors make such observations.Comment: final version to appear in Astroparticle Physic

The Burden of Revision Sinonasal Surgery in the UK – Data from the Chronic Rhinosinusitis Epidemiology Study (CRES); a cross sectional study

Objectives/Hypothesis The aim of this study was to investigate the surgical revision rate in patients with Chronic Rhinosinusitis (CRS) in the UK CRS Epidemiology Study (CRES). Previous evidence from national Sinonasal Audit showed that 1459 CRS patients demonstrated a surgical revision rate 19.1% at 5 years, with highest rates seen in those with polyps (20.6%). Setting Thirty secondary care centres around the UK. Participants A total of 221 controls and 1249 patients with CRS were recruited to the study including those with polyps (CRSwNPs), without polyps (CRSsNPs) and with allergic fungal rhinosinusitis (AFRS). Interventions Self-administered questionnaire. Primary outcome measure The need for previous sinonasal surgery. Results A total of 651 patients with CRSwNPs, 553 with CRSsNPs and 45 with AFRS were included. A total of 396 (57%) of patients with CRSwNPs/AFRS reported having undergone previous endoscopic nasal polypectomy (ENP), of which 182 of the 396 (46%) reported having received more than one operation. The mean number of previous surgeries per patient in the revision group was 3.3 (range 2 to 30) and a mean duration of time of 10 years since the last procedure. The average length of time since their first operation up to inclusion in the study was 15.5 years (range 0-74). Only 27.9% of all patients reporting a prior ENP had received concurrent endoscopic sinus surgery (ESS) (n=102). For comparison, surgical rates in patients with CRSsNPs were significantly lower; 13% of cases specifically reported ESS and of those only 30% reported multiple procedures (chi-squared p < 0.001). Conclusions This study demonstrated there is a high burden of both primary and revision surgery in patients with CRS, worst in those with AFRS and least in those with CRSsNPs. The burden of revision surgery appears unchanged in the decade since the Sinonasal Audit