The goal of this study is to develop a novel electrochemical S-nitrosothiol (RSNO) sensing system with an optimized detection limit and to finalize the specifications required to build a practical RSNO tool for clinical diagnostic applications. RSNO's are a primary carrier and reservoir of NO in vivo and are a potential pre-symptom marker for hypertensive disorders, endothelial dysfunction, cardiovascular risk and inflammation. However, the clinical significance of endogenous RSNO levels cannot be fully realized as a vascular diagnostic tool or biomarker without a quick and convenient assay for RSNO's. Compared to existing RSNO assay techniques, the proposed electrochemical RSNO sensor is highly sensitive and selective, is capable of rapidly measuring RSNO's in blood without separation or pretreatments and is suitable for simple and robust point-of-care use as a clinical diagnostic. A novel catalytic membrane will be prepared by covalently modifying cellulose dialysis membranes with selenocystamine to enhance the sensitivity of the RSNO sensor. The design parameters, including appropriate blood dilution ratios, light protection, temperature control, sensor/reagent stability and the tolerance to varying levels of blood components (e.g. hematocrit/hemoglobin) will be determined in Phase I and will serve as the criteria to build and validate the prototype point-of-care RSNO assay that will be assessed as a biomarker for pulmonary arterial hypertension (PAH) in Phase II.
The goal in this grant is to develop a novel electrochemical S-nitrosothiol (RSNO) sensor with enhanced limit of detection, and to determine the specifications to use this RSNO sensor as the detector to build a practical RSNO analyzer for clinical diagnostic applications, first for trial in pulmonary arterial hypertension (PAH). Currently there is no quick and convenient technique to measure endogenous RSNO concentrations reliably.
|Mottl, Amy K; Buse, John B; Ismail-Beigi, Faramarz et al. (2018) Long-Term Effects of Intensive Glycemic and Blood Pressure Control and Fenofibrate Use on Kidney Outcomes. Clin J Am Soc Nephrol 13:1693-1702|
|Shah, Hetal S; Morieri, Mario Luca; Marcovina, Santica M et al. (2018) Modulation of GLP-1 Levels by a Genetic Variant That Regulates the Cardiovascular Effects of Intensive Glycemic Control in ACCORD. Diabetes Care 41:348-355|
|Morieri, Mario Luca; Gao, He; Pigeyre, Marie et al. (2018) Genetic Tools for Coronary Risk Assessment in Type 2 Diabetes: A Cohort Study From the ACCORD Clinical Trial. Diabetes Care 41:2404-2413|
|Hughes, Timothy M; Sink, Kaycee M; Williamson, Jeff D et al. (2018) Relationships between cerebral structure and cognitive function in African Americans with type 2 diabetes. J Diabetes Complications 32:916-921|
|Chow, Lisa S; Zmora, Rachel; Ma, Sisi et al. (2018) Development of a model to predict 5-year risk of severe hypoglycemia in patients with type 2 diabetes. BMJ Open Diabetes Res Care 6:e000527|
|Freedman, Barry I; Sink, Kaycee M; Hugenschmidt, Christina E et al. (2017) Associations of Early Kidney Disease With Brain Magnetic Resonance Imaging and Cognitive Function in African Americans With Type 2 Diabetes Mellitus. Am J Kidney Dis 70:627-637|
|Murray, Anne M; Hsu, Fang-Chi; Williamson, Jeff D et al. (2017) ACCORDION MIND: results of the observational extension of the ACCORD MIND randomised trial. Diabetologia 60:69-80|
|Coca, Steven G; Nadkarni, Girish N; Huang, Yuan et al. (2017) Plasma Biomarkers and Kidney Function Decline in Early and Established Diabetic Kidney Disease. J Am Soc Nephrol 28:2786-2793|
|Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Eye Study Group and the Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Study Group (2016) Persistent Effects of Intensive Glycemic Control on Retinopathy in Type 2 Diabetes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Follow-On Study. Diabetes Care 39:1089-100|
|Barzilay, Joshua I; Morgan, Timothy M; Murray, Anne M et al. (2016) Brain MRI Volume Findings in Diabetic Adults With Albuminuria: The ACCORD-MIND Study. J Gerontol A Biol Sci Med Sci 71:803-10|
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