Chronic adjunctive trimazosin vasodilator therapy in heart failure: A six month double-blind placebo controlled randomized trial

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24141/1/0000398.pd

Simultaneous Quantitation of Oxidized and Reduced Glutathione via LC-MS/MS: An Insight into the Redox State of Hematopoietic Stem Cells

Cellular redox balance plays a significant role in the regulation of hematopoietic stem-progenitor cell (HSC/MPP) self-renewal and differentiation. Unregulated changes in cellular redox homeostasis are associated with the onset of most hematological disorders. However, accurate measurement of the redox state in stem cells is difficult because of the scarcity of HSC/MPPs. Glutathione (GSH) constitutes the most abundant pool of cellular antioxidants. Thus, GSH metabolism may play a critical role in hematological disease onset and progression. A major limitation to studying GSH metabolism in HSC/MPPs has been the inability to measure quantitatively GSH concentrations in small numbers of HSC/MPPs. Current methods used to measure GSH levels not only rely on large numbers of cells, but also rely on the chemical/structural modification or enzymatic recycling of GSH and therefore are likely to measure only total glutathione content accurately. Here, we describe the validation of a sensitive method used for the direct and simultaneous quantitation of both oxidized and reduced GSH via liquid chromatography followed by tandem mass spectrometry (LC-MS/MS) in HSC/MPPs isolated from bone marrow. The lower limit of quantitation (LLOQ) was determined to be 5.0 ng/mL for GSH and 1.0 ng/mL for GSSG with lower limits of detection at 0.5 ng/mL for both glutathione species. Standard addition analysis utilizing mouse bone marrow shows that this method is both sensitive and accurate with reproducible analyte recovery. This method combines a simple extraction with a platform for the high-throughput analysis, allows for efficient determination of GSH/GSSG concentrations within the HSC/MPP populations in mouse, chemotherapeutic treatment conditions within cell culture, and human normal/leukemia patient samples. The data implicate the importance of the modulation of GSH/GSSG redox couple in stem cells related diseases

Strengthening effective government-citizen connections through greater civic engagement

Citizens are more trusting of government since the terrorist attacks of September 11, 2001, but their civic behaviors are little changed. One reason is that they mostly have been asked for monetary gifts to fund disaster relief and to serve others through existing nonprofit organizations. Available theoretical and empirical analyses suggest the three factors of motivation, skills, and network connections contribute to increased civic engagement, which is defined by behaviors such as seeking to persuade others to join in mobilizing commitment and resources to address a collective problem. Responses to 9/11 have not addressed these three factors. Increased civic engagement strengthens democracy and can contribute to the development of public judgment, which is critical to sustaining support of efforts to thwart terrorism. Success in any effort to increase civic engagement requires different strategies and actions by public officials