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| Investigating Secondary Aerosol Processes in the Amazon through Molecular-Level Characterization of Semi-Volatile Organics | |
| 项目编号 | DE-SC0014040 |
| Goldstein, Allen | |
| 项目主持机构 | The Regents of University of California |
| 开始日期 | 2015-07-15 |
| 结束日期 | 2019-07-14 |
| 英文摘要 | Abstract: Chronic rhinosinusitis (CRS) is estimated to affect 13% of the US population, with annual health care direct costs of nearly $10 billion per year, yet there are few effective therapies for CRS. Detection of Staphylococcus aureus and/or Pseudomonas aeruginosa biofilm in the sinus mucosa is associated with severe CRS presentation. Healthy cells that line the nasal passages normally emit significant levels of nitric oxide (NO), a potent and natural antimicrobial molecule that stimulates mucociliary clearance and reduces bacterial biofilm formation. Reduced levels of NO in the exhaled nasal breath of CRS patients suggest that boosting local NO concentrations within the sinuses may be quite beneficial. In Phase I of this project, NOTA Laboratories, LLC, clearly demonstrated that a naturally occurring and inexpensive NO releasing agent, S-nitrosoglutathione (GSNO), can be incorporated into a typical saline/bicarbonate sinus rinse solution and generate adequate levels of NO to significantly reduce levels of live bacteria counts for two biofilm forming CRS microbes (S. aureus and P. aeruginosa). In these experiments, the bacterial biofilms were grown on the surface of human upper airway epithelial cells. We further demonstrated that the levels of GSNO and concomitant NO released do not harm the underlying human cells, as assessed by monitoring the levels of a toxicity-associated cytokine (IL-8). In addition, NOTA demonstrated that the release rates of NO from GSNO can be enhanced by the presence of ascorbate (Asc; vitamin C) and that the resulting powder formulations of GSNO/Asc can be stored for more than 6 months (at 37 °C) while retaining >80% of their NO release capability. Via Phase II SBIR funding, NOTA will: 1) Further optimize the concentration of the GSNO/Asc mixture within an isotonic NaCl/NaHCO3/EDTA solution and frequency of application for the in vitro disruption of S. aureus and P. aeruginosa biofilms formed on human upper airway epithelial cells over 3 d test periods; 2) Explore a commercial packaging process (in polymer film lined aluminum pouches) and test the resulting 1-year stability of a dry packaged GSNO/Asc/NaCl/NaHCO3/EDTA mixed powder that will be reconstituted in plastic sinus flush bottles with 240 mL of pure water immediately before use by patients; 3) Conduct animal studies in rabbits to determine if NOTA's reconstituted RSNO/Asc/NaCl/NaHCO3/EDTA formulation, given as an aerosol spray twice daily over a 7 d period, significantly decreases bacterial counts in the sinus cavities of infected rabbits (with CRS) vs. controls (only NaCl/NaHCO3/EDTA); and 4) Begin the regulatory process by obtaining expert assessments of the role of the FDA in approval of the new GSNO formulations as a potential over-the-counter product for the CRS market. The completion of these efforts during Phase II will enable NOTA to plan the first human subject clinical trials at the University of Michigan Sinus Center as part of Phase III studies. |
| 英文关键词 | Water;Visit;Universities;treatment duration;Toxic effect;Time;Testing;Test Result;Technology;Surface;Staphylococcus aureus;Specialist;Small Business Innovation Research Grant;Sinus;Saline;S-Nitrosothiols;S-Nitrosoglutathione;Role;Risk;rhinosinusitis;Research;Reducing Agents;reconstitution;Pseudomonas aeruginosa;Productivity;product development;Process;Prevention;prevent;pre-clinical;Powder dose form;Population;Polymers;Plasticizers;phase 3 study;phase 1 study;Phase;Pharmaceutical Preparations;Pennsylvania;Patients;Oryctolagus cuniculus;Nose;Nitric Oxide;natural antimicrobial;Mucous Membrane;Mucociliary Clearance;Monitor;Modeling;Microbial Biofilms;microbial;Microbe;Michigan;Measures;Literature;Laboratory Animal Medicine;Laboratories;Isotonic Exercise;innovative technologies;Individual;in vivo;In Vitro;improved;IL8 gene;human subject;Human;Hour;Histologic;Healthcare;Glutathione;Generations;Funding;Frequencies;Formulation;Flushing;Film;Expert Opinion;experimental study;Exhibits;Exhalation;Epithelial Cells;Effectiveness;effective therapy;Edetic Acid;economic impact;Dose;Disease;Direct Costs;Detection;Data;cytokine;cost;Common Cold;Clinical Trials;chronic rhinosinusitis;Cells;Cell Line;Blood Circulation;Blood;Bicarbonates;base;Bacterial Counts;Bacteria;Ascorbic Acid;ascorbate;Antiviral Agents;Antimicrobial Effect;antimicrobial drug;antimicrobial;Antibiotics;Animals;Animal Experiments;Aluminum;Affect;Aerosols;Adult |
| 学科分类 | 09 - 环境科学;06 - 生物科学 |
| 资助机构 | US-DOE |
| 项目经费 | 796765 |
| 项目类型 | Grant |
| 国家 | US |
| 语种 | 英语 |
| 文献类型 | 项目 |
| 条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/74146 |
| 推荐引用方式 GB/T 7714 | Goldstein, Allen.Investigating Secondary Aerosol Processes in the Amazon through Molecular-Level Characterization of Semi-Volatile Organics.2015. |
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