Salivary Metabolomics of Well and Poorly Controlled Type 1 and Type 2 Diabetes

Objective. The concentrations of endogenous metabolites in saliva can be altered based on the systemic condition of the hosts and may, in theory, serve as a reflection of systemic disease progression. Hemoglobin A1C is used clinically to measure long-term average glycemic control. The aim of the study was to demonstrate if there were differences in the salivary metabolic profiles between well and poorly controlled type 1 and type 2 subjects with diabetes. Subjects and Methods. Subjects with type 1 and type 2 diabetes were enrolled (n = 40). The subjects were assigned to phenotypic groups based on their current level of A1C: 7 = poorly controlled. Demographic data, age, gender, and ethnicity, were used to match the two phenotypic groups. Whole saliva samples were collected and immediately stored at -80°C. Samples were spiked using an isotopically labeled internal standard and analyzed by UPLC-TOF-MS using a Waters SYNAPT G2-Si mass spectrometer. Results. Unsupervised principal components analysis (PCA) and orthogonal partial least squares regression discrimination analysis (OPLS-DA) were used to define unique metabolomic profiles associated with well and poorly controlled diabetes based on A1C levels. Conclusion. OPLS-DA demonstrates good separation of well and poorly controlled in both type 1 and type 2 diabetes. This provides evidence for developing saliva-based monitoring tools for diabetes

Self-referencing Mach-Zehnder interferometer as a laser system diagnostic: Active and adaptive optical systems

We are incorporating a novel self-referencing Mach-Zehnder interferometer into a large scale laser system as a real time, interactive diagnostic tool for wavefront measurement. The instrument is capable of absolute wavefront measurements accurate to better than {lambda}/10 pv over a wavelength range > 300 nm without readjustment of the optical components. This performance is achieved through the design of both refractive optics and catadioptric collimator to achromatize the Mach-Zehnder reference arm. Other features include polarization insensitivity through the use of low angles of incidence on all beamsplitters as well as an equal path length configuration that allows measurement of either broad-band or closely spaced laser-line sources. Instrument accuracy is periodically monitored in place by means of a thermally and mechanically stable wavefront reference source that is calibrated off-line with a phase conjugate interferometer. Video interferograms are analyzed using Fourier transform techniques on a computer that includes dedicated array processor. Computer and video networks maintain distributed interferometers under the control of a single analysis computer with multiple user access. 7 refs., 11 figs

Intracellular innate resistance to bacterial pathogens

Mammalian innate immunity stimulates antigen-specific immune responses and acts to control infection prior to the onset of adaptive immunity. Some bacterial pathogens replicate within the host cell and are therefore sheltered from some protective aspects of innate immunity such as complement. Here we focus on mechanisms of innate intracellular resistance encountered by bacterial pathogens and how some bacteria can evade destruction by the innate immune system. Major strategies of intracellular antibacterial defence include pathogen compartmentalization and iron limitation. Compartmentalization of pathogens within the host endocytic pathway is critical for generating high local concentrations of antimicrobial molecules, such as reactive oxygen species, and regulating concentrations of divalent cations that are essential for microbial growth. Cytosolic sensing, autophagy, sequestration of essential nutrients and membrane attack by antimicrobial peptides are also discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71916/1/j.1462-5822.2006.00795.x.pd