Browsing by Author "Nichols, Scott P"
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Item Open Access Antibiotic-induced changes in the microbiota disrupt redox dynamics in the gut.(eLife, 2018-06-19) Reese, Aspen T; Cho, Eugenia H; Klitzman, Bruce; Nichols, Scott P; Wisniewski, Natalie A; Villa, Max M; Durand, Heather K; Jiang, Sharon; Midani, Firas S; Nimmagadda, Sai N; O'Connell, Thomas M; Wright, Justin P; Deshusses, Marc A; David, Lawrence AHow host and microbial factors combine to structure gut microbial communities remains incompletely understood. Redox potential is an important environmental feature affected by both host and microbial actions. We assessed how antibiotics, which can impact host and microbial function, change redox state and how this contributes to post-antibiotic succession. We showed gut redox potential increased within hours of an antibiotic dose in mice. Host and microbial functioning changed under treatment, but shifts in redox potentials could be attributed specifically to bacterial suppression in a host-free ex vivo human gut microbiota model. Redox dynamics were linked to blooms of the bacterial family Enterobacteriaceae. Ecological succession to pre-treatment composition was associated with recovery of gut redox, but also required dispersal from unaffected gut communities. As bacterial competition for electron acceptors can be a key ecological factor structuring gut communities, these results support the potential for manipulating gut microbiota through managing bacterial respiration.Item Open Access Injectable Phosphorescence-based Oxygen Biosensors Identify Post Ischemic Reactive Hyperoxia.(Scientific reports, 2017-08-15) Chien, Jennifer S; Mohammed, Mahmoud; Eldik, Hysem; Ibrahim, Mohamed M; Martinez, Jeremy; Nichols, Scott P; Wisniewski, Natalie; Klitzman, BruceNovel injectable biosensors were used to measure interstitial oxygenation before, during, and after transient ischemia. It is well known that reactive hyperemia occurs following a period of ischemia. However, increased blood flow does not necessarily mean increased oxygen tension in the tissue. Therefore, the purpose of this study was to test the hypothesis that tissue reactive hyperoxia occurs following release of hind-limb tourniquet occlusions. Rats were injected with bilateral hind-limb biosensors and were simultaneously subjected to a unilateral femoral vessel ligation. After approximately one and three months, the rats underwent a series of oxygenation challenges, including transient hind-limb tourniquet occlusion. Along with the biosensors, near infrared spectroscopy was used to measure percent oxyhemoglobin in capillaries and laser Doppler flowmetry was used to measure blood flow. Post-occlusion reactive hyperemia was observed. It was accompanied by tissue reactive hyperoxia, affirming that the post-occlusion oxygen supply must have exceeded the expected increased oxygen consumption. The measurement of the physiologic phenomenon of reactive hyperoxia could prove clinically beneficial for both diagnosis and optimizing therapy.Item Open Access The effect of nitric oxide surface flux on the foreign body response to subcutaneous implants.(Biomaterials, 2012-09) Nichols, Scott P; Koh, Ahyeon; Brown, Nga L; Rose, Michael B; Sun, Bin; Slomberg, Danielle L; Riccio, Daniel A; Klitzman, Bruce; Schoenfisch, Mark HAlthough the release of nitric oxide (NO) from biomaterials has been shown to reduce the foreign body response (FBR), the optimal NO release kinetics and doses remain unknown. Herein, polyurethane-coated wire substrates with varying NO release properties were implanted into porcine subcutaneous tissue for 3, 7, 21 and 42 d. Histological analysis revealed that materials with short NO release durations (i.e., 24 h) were insufficient to reduce the collagen capsule thickness at 3 and 6 weeks, whereas implants with longer release durations (i.e., 3 and 14 d) and greater NO payloads significantly reduced the collagen encapsulation at both 3 and 6 weeks. The acute inflammatory response was mitigated most notably by systems with the longest duration and greatest dose of NO release, supporting the notion that these properties are most critical in circumventing the FBR for subcutaneous biomedical applications (e.g., glucose sensors).Item Open Access Tissue-Integrating Oxygen Sensors: Continuous Tracking of Tissue Hypoxia.(Advances in experimental medicine and biology, 2017-01) Wisniewski, Natalie A; Nichols, Scott P; Gamsey, Soya J; Pullins, Steve; Au-Yeung, Kit Y; Klitzman, Bruce; Helton, Kristen LWe describe a simple method of tracking oxygen in real-time with injectable, tissue-integrating microsensors. The sensors are small (500 μm × 500 μm × 5 mm), soft, flexible, tissue-like, biocompatible hydrogel s that have been shown to overcome the foreign body response for long-term sensing. The sensors are engineered to change luminescence in the presence of oxygen or other analytes and function for months to years in the body. A single injection followed by non-invasive monitoring with a hand-held or wearable Bluetooth optical reader enables intermittent or continuous measurements. Proof of concept for applications in high altitude, exercise physiology, vascular disease, stroke, tumors, and other disease states have been shown in mouse, rat and porcine models. Over 90 sensors have been studied to date in humans. These novel tissue-integrating sensors yield real-time insights in tissue oxygen fluctuations for research and clinical applications.