Sitagliptin reduces cardiac apoptosis, hypertrophy and fibrosis primarily by insulin-dependent mechanisms in experimental type-II diabetes. Potential roles of GLP-1 isoforms

Background:Myocardial fibrosis is a key process in diabetic cardiomyopathy. However, their underlying mechanisms have not been elucidated, leading to a lack of therapy. The glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, reduces hyperglycemia but may also trigger direct effects on the heart.Methods:Goto-Kakizaki (GK) rats developed type-II diabetes and received sitagliptin, an anti-hyperglycemic drug (metformin) or vehicle (n=10, each). After cardiac structure and function assessment, plasma and left ventricles were isolated for biochemical studies. Cultured cardiomyocytes and fibroblasts were used for in vitro assays.Results:Untreated GK rats exhibited hyperglycemia, hyperlipidemia, plasma GLP-1 decrease, and cardiac cell-death, hypertrophy, fibrosis and prolonged deceleration time. Moreover, cardiac pro-apoptotic/necrotic, hypertrophic and fibrotic factors were up-regulated. Importantly, both sitagliptin and metformin lessened all these parameters. In cultured cardiomyocytes and cardiac fibroblasts, high-concentration of palmitate or glucose induced cell-death, hypertrophy and fibrosis. Interestingly, GLP-1 and its insulinotropic-inactive metabolite, GLP-1(9-36), alleviated these responses. In addition, despite a specific GLP-1 receptor was only detected in cardiomyocytes, GLP-1 isoforms attenuated the pro-fibrotic expression in cardiomyocytes and fibroblasts. In addition, GLP-1 receptor signalling may be linked to PPARδ activation, and metformin may also exhibit anti-apoptotic/necrotic and anti-fibrotic direct effects in cardiac cells.Conclusions:Sitagliptin, via GLP-1 stabilization, promoted cardioprotection in type-II diabetic hearts primarily by limiting hyperglycemia e hyperlipidemia. However, GLP-1 and GLP-1(9-36) promoted survival and anti-hypertrophic/fibrotic effects on cultured cardiac cells, suggesting cell-autonomous cardioprotective actionsThis work was supported by national funding from Ministerio de Educación y Ciencia (SAF2009-08367), Comunidad de Madrid (CCG10-UAM/ BIO-5289), and a unrestricted grant from by Merck/MS

Prevalence of comorbidities and baseline characteristics of LAP-BAND AP subjects in the Helping Evaluate Reduction in Obesity (HERO) study

OBJECTIVE: To describe the baseline characteristics in patients who chose placement of a LAP-BAND AP® System (LBAP) and participated in the Helping Evaluate Reduction in Obesity (HERO) Study across regions. PATIENTS AND METHODS: HERO is a five- year, prospective, multicenter, international study of patients with LBAP placement between July 22, 2009 and January 31, 2011. In addition to baseline and peri-surgery clinical data, seven follow up visits are scheduled at 3, 6 and 12 months, and annually through year five. Data collection included family and medical history, clinical outcomes, laboratory data, health-related quality of life (HRQoL), productivity, healthcare resource utilization, and adverse events. RESULTS: LBAP were placed in 1106 enrolled patients; 56.6% from the US, 26.3% from Europe, 7.1% from Canada, and 10.0% from Australia. The majority were female (n = 877 (79.3%)) with a mean age of 43 years (s.d. = 11.4) and mean body mass index of 45.1 kg/m(2) (s.d. = 6.9). The most common comorbidities were hypertension (HTN) (overall  = 42.9%) and diabetes (overall 22.2%, with 27% from the US and 14% from Europe). Overall, less than 5% had a history of cardiovascular disease. The prevalence rates of HTN, diabetes and cardiovascular disease were significantly (p<0.001) higher in men than in women across all regions. Overall HRQoL also worsened with increasing BMI. CONCLUSIONS: The HERO study is the first large, multinational and long-term registry with the LBAP. This study will provide real-world outcomes data on LAGB that will help inform patient choice, clinician treatment strategies, and payer reimbursement decisions

“No One Gets Left Behind:” Managing Library Human Resources During Dramatic Shifts in Academic Libraries

To be published in Advances in Library Administration and Organization (Vol 33, 2015)One of the greatest challenges facing academic libraries is maintaining necessary space for collections and services. Academic administrators are forced to balance the need for space to support new and expanded programs, while supporting the traditional needs of the educational enterprise. With many of these situations, the answer comes from redeploying library space for other purposes. The net result for libraries is that functions and services run for years might no longer be possible with these changes in space. This is exactly the problem faced by the Kresge Business Administration Library at the University of Michigan when a major gift led to a construction project that saw the library’s footprint decrease by over 80%. As Kresge went through this change, there was a concerted effort to retain jobs, even though many would be dramatically changed with the new world order. This chapter focuses on the response undertaken at Kresge Library to balance the changing needs of the library that accompany dramatic space reduction. Additionally, this chapter will explore the literature on staffing trends in light of major changes to our work, political posturing to generate more work or ‘business’ for library staff, exploration of the assessment program to ensure that we have the right staffing levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111739/1/Seeman_2015_AdvancesinLibraryAdministrationOrganization_Revised.docxDescription of Seeman_2015_AdvancesinLibraryAdministrationOrganization_Revised.docx : Word Documen