BACKGROUND In 2008, the US Food and Drug Administration (FDA) issued a Guidance for Industry statement formally recognizing (during drug development) the conjoined nature of type 2 diabetes (T2D) and cardiovascular disease (CVD), which has precipitated an urgent need for panels of markers (and means of analysis) that are able to differentiate subtypes of CVD in the context of T2D. Here, we explore the possibility of creating such panels using the working hypothesis that proteins, in addition to carrying time-cumulative marks of hyperglycemia (e.g., protein glycation in the form of Hb A1c), may carry analogous information with regard to systemic oxidative stress and aberrant enzymatic signaling related to underlying pathobiologies involved in T2D and/or CVD. METHODS We used mass spectrometric immunoassay to quantify, in targeted fashion, relative differences in the glycation, oxidation, and truncation of 11 specific proteins. RESULTS Protein oxidation and truncation (owing to modified enzymatic activity) are able to distinguish between subsets of diabetic patients with or without a history of myocardial infarction and/or congestive heart failure where markers of glycation alone cannot. CONCLUSION Markers based on protein modifications aligned with the known pathobiologies of T2D represent a reservoir of potential cardiovascular markers that are needed to develop the next generation of antidiabetes medications.

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The C22 and C276 alloy metal surfaces were characterized for electrochemical activity in alkaline aqueous media in the presence and absence of oxygen (O 2 ) and at 30° C. The metal was studied by electrochemical impedance spectroscopy (EIS), voltammetry with a still electrode and a specialized rotating ring-disk electrode (RRDE) technique, the cyclic potential ring measurement (CPRM) method (1). The CPRM method gave the steady state O 2 reduction kinetics. An initial study of O 2 reduction on gold yielded virtually identical results to the work of Vilambi and Taylor who first described the CPRM method. The application of the CPRM method to the study of O 2 reduction on C22 and C276 showed strong evidence for a predominantly series 2 step, 2 electron O 2 reduction pathway, where kinetic rate constants k 2 (evaluated at -0.7V versus the saturated calomel electrode) and k 3 (evaluated at -1.2V) were estimated at 30° C to be 0.001 cm/s and 0.193 cm/s respectively for C22 and 0.013 cm/s and 0.232 cm/s respectively for C276.

Introduction Analysis of biological samples for volatile organic compound (VOC) profiles or fingerprints can potentially be utilized as a non-invasive, early stage diagnostic tool for disease related to metabolic processes. A hypothesis was presented in 1989 that dogs could detect malignant tumors by scent and several studies of canine scent detection for cancer followed. Our team has taken an analogous approach using solid phase microextraction in combination with capillary gas chromatography time of flight mass spectrometry (SPME GC-TOFMS) in place of canine scent detection to discover indicators for pancreatic cancer, a deadly cancer difficult to detect in its early development stage. VOCs are not commonly considered in “biomarker” analysis of clinical samples which usually require extensive pre-processing. The VOC fingerprint from a biological sample presumes many such substances are products, by-products, and waste resulting from human metabolism (and/or symbiotic microbiom) of nutrients and intermediates from endogenous processes, absorbed environmental contaminants, and endo/exogenous bacterial metabolism. Methods IRB approval was obtained to enroll patients with advanced pancreatic cancer and healthy volunteers. Blood was collected in pre-conditioned vacutainers from 11 patients and 5 healthy volunteers, all non-smokers, no chemotherapy in preceding 5 days, and analyzed within 2 weeks. SPME GC-TOFMS is a means for eliminating the biological matrix and pre-concentrating specific ranges of complex volatile fraction polarities at low concentrations and a very sensitive analytical instrumental platform for the characterization of VOC chromatographic profiles extracted from the 3ml blood samples. Multivariate statistical methods were used to analysis retention time exact mass observations and integrated peak areas. Results Even with the numerous variables contributing to an already diverse underlying metabolism of each participant, our chemometric approach did discriminate between “healthy” volunteers and the cancer patients with a 5% prediction error using a “leave one out” statistical analysis for 37 samplesb from the 16 subjects. Key retention time and exact mass observations from a fiber specific SPME were associated to preliminary molecule identifications via NIST data base searches. Our procedures for system tune, calibration, and monitoring achieved a response stability over a 1 month period of ∼10% rsd and accurate mass measurement of at least 5 mDa (30 - 300 Da) using benzene-d6, BFB, and naphthalene-d8. Conclusions VOC fingerprints from a SPME GC-TOFMS analysis of blood can be successful in discovering differentiating indicators related to APC. Future work will involve other SPME fibers and more samples. (Supported by the IBIS & Scottsdale Health Care Foundations) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1264. doi:1538-7445.AM2012-1264

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